Induction of intestinal lymphoid tissue formation by intrinsic and extrinsic signals (original) (raw)

• Brandtzaeg P, Pabst R (2004) Let's go mucosal: communication on slippery ground. Trends Immunol 25:570–577. doi:10.1016/j.it.2004.09.005
  Article CAS PubMed Google Scholar
• Bouskra D, Brezillon C, Berard M, Werts C, Varona R, Boneca IG, Eberl G (2008) Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature 456:507–510. doi:10.1038/nature07450
  Article CAS PubMed Google Scholar
• Pabst O, Herbrand H, Friedrichsen M, Velaga S, Dorsch M, Berhardt G, Worbs T, Macpherson AJ, Forster R (2006) Adaptation of solitary intestinal lymphoid tissue in response to microbiota and chemokine receptor CCR7 signaling. J Immunol 177:6824–6832
  CAS PubMed Google Scholar
• Tsuji M, Suzuki K, Kitamura H, Maruya M, Kinoshita K, Ivanov II, Itoh K, Littman DR, Fagarasan S (2008) Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulin a generation in the gut. Immunity 29:261–271. doi:10.1016/j.immuni.2008.05.014
  Article CAS PubMed Google Scholar
• Mebius RE (2003) Organogenesis of lymphoid tissues. Nat Rev Immunol 3:292–303. doi:10.1038/nri1054
  Article CAS PubMed Google Scholar
• Nishikawa S, Honda K, Vieira P, Yoshida H (2003) Organogenesis of peripheral lymphoid organs. Immunol Rev 195:72–80. doi:10.1034/j.1600-065X.2003.00063.x
  Article CAS PubMed Google Scholar
• Aloisi F, Pujol-Borrell R (2006) Lymphoid neogenesis in chronic inflammatory diseases. Nat Rev Immunol 6:205–217. doi:10.1038/nri1786
  Article CAS PubMed Google Scholar
• Drayton DL, Liao S, Mounzer RH, Ruddle NH (2006) Lymphoid organ development: from ontogeny to neogenesis. Nat Immunol 7:344–353. doi:10.1038/ni1330
  Article CAS PubMed Google Scholar
• Spencer J, MacDonald TT, Finn T, Isaacson PG (1986) The development of gut associated lymphoid tissue in the terminal ileum of fetal human intestine. Clin Exp Immunol 64:536–543
  CAS PubMed Google Scholar
• Cornes JS (1965) Peyer's patches in the human gut. Proc R Soc Med 58:716
  CAS PubMed Google Scholar
• Mutwiri G, Watts T, Lew L, Beskorwayne T, Papp Z, Baca-Estrada ME, Griebel P (1999) Ileal and jejunal Peyer's patches play distinct roles in mucosal immunity of sheep. Immunology 97:455–461. doi:10.1046/j.1365-2567.1999.00791.x
  Article CAS PubMed Google Scholar
• Pabst R, Reynolds JD (1987) Peyer's patches export lymphocytes throughout the lymphoid system in sheep. J Immunol 139:3981–3985
  CAS PubMed Google Scholar
• Yasuda M, Nasu T, Murakami T (2009) Differential cytokine mRNA expression in single lymphatic follicles of the calf ileal and jejunal Peyer's patches. Dev Comp Immunol 33:430–433. doi:10.1016/j.dci.2008.09.007
  Article CAS PubMed Google Scholar
• Crabbe PA, Nash DR, Bazin H, Eyssen H, Heremans JF (1970) Observations on lymphoid tissues from conventional and germ free mice. Lab Invest 22:448
  CAS PubMed Google Scholar
• Iwasaki A, Kelsall BL (2000) Localization of distinct Peyer's patch dendritic cell subsets and their recruitment by chemokines macrophage inflammatory protein (MIP)-3alpha, MIP-3beta, and secondary lymphoid organ chemokine. J Exp Med 191:1381–1394. doi:10.1084/jem.191.8.1381
  Article CAS PubMed Google Scholar
• Salazar-Gonzalez RM, Niess JH, Zammit DJ, Ravindran R, Srinivasan A, Maxwell JR, Stoklasek T, Yadav R, Williams IR, Gu X, McCormick BA, Pazos MA, Vella AT, Lefrancois L, Reinecker HC, McSorley SJ (2006) CCR6-mediated dendritic cell activation of pathogen-specific T cells in Peyer's patches. Immunity 24:623–632. doi:10.1016/j.immuni.2006.02.015
  Article CAS PubMed Google Scholar
• Iwasaki A, Kelsall BL (2001) Unique functions of CD11b+, CD8 alpha+, and double-negative Peyer's patch dendritic cells. J Immunol 166:4884–4890
  CAS PubMed Google Scholar
• Yamanaka T, Helgeland L, Farstad IN, Fukushima H, Midtvedt T, Brandtzaeg P (2003) Microbial colonization drives lymphocyte accumulation and differentiation in the follicle-associated epithelium of Peyer's patches. J Immunol 170:816–822
  CAS PubMed Google Scholar
• Tsuji M, Komatsu N, Kawamoto S, Suzuki K, Kanagawa O, Honjo T, Hori S, Fagarasan S (2009) Preferential generation of follicular B helper T cells from Foxp3+ T cells in gut Peyer's patches. Science 323:1488–1492. doi:10.1126/science.1169152
  Article CAS PubMed Google Scholar
• Cerutti A, Rescigno M (2008) The biology of intestinal immunoglobulin A responses. Immunity 28:740–750. doi:10.1016/j.immuni.2008.05.001
  Article CAS PubMed Google Scholar
• Hamada H, Hiroi T, Nishiyama Y, Takahashi H, Masunaga Y, Hachimura S, Kaminogawa S, Takahashi-Iwanaga H, Iwanaga T, Kiyono H, Yamamoto H, Ishikawa H (2002) Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine. J Immunol 168:57–64
  CAS PubMed Google Scholar
• Lorenz RG, Chaplin DD, McDonald KG, McDonough JS, Newberry RD (2003) Isolated lymphoid follicle formation is inducible and dependent upon lymphotoxin-sufficient B lymphocytes, lymphotoxin beta receptor, and TNF receptor I function. J Immunol 170:5475–5482
  CAS PubMed Google Scholar
• Ivanov II, Diehl GE, Littman DR (2006) Lymphoid tissue inducer cells in intestinal immunity. Curr Top Microbiol Immunol 308:59–82. doi:10.1007/3-540-30657-9_3
  Article CAS PubMed Google Scholar
• Glaysher BR, Mabbott NA (2007) Isolated lymphoid follicle maturation induces the development of follicular dendritic cells. Immunology 120:336–344. doi:10.1111/j.1365-2567.2006.02508.x
  Article CAS PubMed Google Scholar
• Lorenz RG, Newberry RD (2004) Isolated lymphoid follicles can function as sites for induction of mucosal immune responses. Ann N Y Acad Sci 1029:44–57. doi:10.1196/annals.1309.006
  Article CAS PubMed Google Scholar
• Kanamori Y, Ishimaru K, Nanno M, Maki K, Ikuta K, Nariuchi H, Ishikawa H (1996) Identification of novel lymphoid tissues in murine intestinal mucosa where clusters of c-kit + IL-7R + Thy1+ lympho-hemopoietic progenitors develop. J Exp Med 184:1449–1459. doi:10.1084/jem.184.4.1449
  Article CAS PubMed Google Scholar
• Pabst O, Herbrand H, Worbs T, Friedrichsen M, Yan S, Hoffmann MW, Korner H, Bernhardt G, Pabst R, Forster R (2005) Cryptopatches and isolated lymphoid follicles: dynamic lymphoid tissues dispensable for the generation of intraepithelial lymphocytes. Eur J Immunol 35:98–107. doi:10.1002/eji.200425432
  Article CAS PubMed Google Scholar
• Kraehenbuhl JP, Neutra MR (2000) Epithelial M cells: differentiation and function. Annu Rev Cell Dev Biol 16:301–332. doi:10.1146/annurev.cellbio.16.1.301
  Article CAS PubMed Google Scholar
• Sierro F, Pringault E, Assman PS, Kraehenbuhl JP, Debard N (2000) Transient expression of M-cell phenotype by enterocyte-like cells of the follicle-associated epithelium of mouse Peyer's patches. Gastroenterology 119:734–743. doi:10.1053/gast.2000.16481
  Article CAS PubMed Google Scholar
• Gebert A, Rothkotter HJ, Pabst R (1996) M cells in Peyer's patches of the intestine. Int Rev Cytol 167:91–159. doi:10.1016/S0074-7696(08)61346-7
  Article CAS PubMed Google Scholar
• Fotopoulos G, Harari A, Michetti P, Trono D, Pantaleo G, Kraehenbuhl JP (2002) Transepithelial transport of HIV-1 by M cells is receptor-mediated. Proc Natl Acad Sci U S A 99:9410–9414. doi:10.1073/pnas.142586899
  Article CAS PubMed Google Scholar
• Tyrer PC, Ruth Foxwell A, Kyd JM, Otczyk DC, Cripps AW (2007) Receptor mediated targeting of M-cells. Vaccine 25:3204–3209. doi:10.1016/j.vaccine.2007.01.028
  Article CAS PubMed Google Scholar
• Chabot S, Wagner JS, Farrant S, Neutra MR (2006) TLRs regulate the gatekeeping functions of the intestinal follicle-associated epithelium. J Immunol 176:4275–4283
  CAS PubMed Google Scholar
• Gebert A, Steinmetz I, Fassbender S, Wendlandt KH (2004) Antigen transport into Peyer's patches: increased uptake by constant numbers of M cells. Am J Pathol 164:65–72
  PubMed Google Scholar
• Man AL, Prieto-Garcia ME, Nicoletti C (2004) Improving M cell mediated transport across mucosal barriers: do certain bacteria hold the keys? Immunology 113:15–22. doi:10.1111/j.1365-2567.2004.01964.x
  Article CAS PubMed Google Scholar
• Mora JR, Iwata M, Eksteen B, Song SY, Junt T, Senman B, Otipoby KL, Yokota A, Takeuchi H, Ricciardi-Castagnoli P, Rajewsky K, Adams DH, von Andrian UH (2006) Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science 314:1157–1160. doi:10.1126/science.1132742
  Article CAS PubMed Google Scholar
• Sato A, Hashiguchi M, Toda E, Iwasaki A, Hachimura S, Kaminogawa S (2003) CD11b+ Peyer's patch dendritic cells secrete IL-6 and induce IgA secretion from naive B cells. J Immunol 171:3684–3690
  CAS PubMed Google Scholar
• Bjerke K, Brandtzaeg P (1988) Lack of relation between expression of HLA-DR and secretory component (SC) in follicle-associated epithelium of human Peyer's patches. Clin Exp Immunol 71:502–507
  CAS PubMed Google Scholar
• Pappo J, Owen RL (1988) Absence of secretory component expression by epithelial cells overlying rabbit gut-associated lymphoid tissue. Gastroenterology 95:1173–1177
  CAS PubMed Google Scholar
• Mantis NJ, Cheung MC, Chintalacharuvu KR, Rey J, Corthesy B, Neutra MR (2002) Selective adherence of IgA to murine Peyer's patch M cells: evidence for a novel IgA receptor. J Immunol 169:1844–1851
  CAS PubMed Google Scholar
• Kadaoui KA, Corthesy B (2007) Secretory IgA mediates bacterial translocation to dendritic cells in mouse Peyer's patches with restriction to mucosal compartment. J Immunol 179:7751–7757
  CAS PubMed Google Scholar
• Anderle P, Rumbo M, Sierro F, Mansourian R, Michetti P, Roberts MA, Kraehenbuhl JP (2005) Novel markers of the human follicle-associated epithelium identified by genomic profiling and microdissection. Gastroenterology 129:321–327. doi:10.1053/j.gastro.2005.03.044
  Article CAS PubMed Google Scholar
• Hase K, Ohshima S, Kawano K, Hashimoto N, Matsumoto K, Saito H, Ohno H (2005) Distinct gene expression profiles characterize cellular phenotypes of follicle-associated epithelium and M cells. DNA Res 12:127–137. doi:10.1093/dnares/12.2.127
  Article CAS PubMed Google Scholar
• Lo D, Tynan W, Dickerson J, Scharf M, Cooper J, Byrne D, Brayden D, Higgins L, Evans C, O'Mahony DJ (2004) Cell culture modeling of specialized tissue: identification of genes expressed specifically by follicle-associated epithelium of Peyer's patch by expression profiling of Caco-2/Raji co-cultures. Int Immunol 16:91–99. doi:10.1093/intimm/dxh011
  Article CAS PubMed Google Scholar
• Pielage JF, Cichon C, Greune L, Hirashima M, Kucharzik T, Schmidt MA (2007) Reversible differentiation of Caco-2 cells reveals galectin-9 as a surface marker molecule for human follicle-associated epithelia and M cell-like cells. Int J Biochem Cell Biol 39:1886–1901. doi:10.1016/j.biocel.2007.05.009
  Article CAS PubMed Google Scholar
• Verbrugghe P, Waelput W, Dieriks B, Waeytens A, Vandesompele J, Cuvelier CA (2006) Murine M cells express annexin V specifically. J Pathol 209:240–249. doi:10.1002/path.1970
  Article CAS PubMed Google Scholar
• Zhao X, Sato A, Dela Cruz CS, Linehan M, Luegering A, Kucharzik T, Shirakawa AK, Marquez G, Farber JM, Williams I, Iwasaki A (2003) CCL9 is secreted by the follicle-associated epithelium and recruits dome region Peyer's patch CD11b+ dendritic cells. J Immunol 171:2797–2803
  CAS PubMed Google Scholar
• Finke D, Kraehenbuhl JP (2001) Formation of Peyer's patches. Curr Opin Genet Dev 11:561–567. doi:10.1016/S0959-437X(00)00233-1
  Article CAS PubMed Google Scholar
• Izadpanah A, Dwinell MB, Eckmann L, Varki NM, Kagnoff MF (2001) Regulated MIP-3alpha/CCL20 production by human intestinal epithelium: mechanism for modulating mucosal immunity. Am J Physiol Gastrointest Liver Physiol 280:G710–G719
  CAS PubMed Google Scholar
• Kondo T, Takata H, Takiguchi M (2007) Functional expression of chemokine receptor CCR6 on human effector memory CD8+ T cells. Eur J Immunol 37:54–65. doi:10.1002/eji.200636251
  Article CAS PubMed Google Scholar
• Kucharzik T, Hudson JT 3rd, Waikel RL, Martin WD, Williams IR (2002) CCR6 expression distinguishes mouse myeloid and lymphoid dendritic cell subsets: demonstration using a CCR6 EGFP knock-in mouse. Eur J Immunol 32:104–112. doi:10.1002/1521-4141(200201)32:1<104::AID-IMMU104>3.0.CO;2-C
  Article CAS PubMed Google Scholar
• Liao F, Rabin RL, Smith CS, Sharma G, Nutman TB, Farber JM (1999) CC-chemokine receptor 6 is expressed on diverse memory subsets of T cells and determines responsiveness to macrophage inflammatory protein 3 alpha. J Immunol 162:186–194
  CAS PubMed Google Scholar
• Tanaka Y, Imai T, Baba M, Ishikawa I, Uehira M, Nomiyama H, Yoshie O (1999) Selective expression of liver and activation-regulated chemokine (LARC) in intestinal epithelium in mice and humans. Eur J Immunol 29:633–642. doi:10.1002/(SICI)1521-4141(199902)29:02<633::AID-IMMU633>3.0.CO;2-I
  Article CAS PubMed Google Scholar
• Sierro F, Dubois B, Coste A, Kaiserlian D, Kraehenbuhl JP, Sirard JC (2001) Flagellin stimulation of intestinal epithelial cells triggers CCL20-mediated migration of dendritic cells. Proc Natl Acad Sci U S A 98:13722–13727. doi:10.1073/pnas.241308598
  Article CAS PubMed Google Scholar
• Cook DN, Prosser DM, Forster R, Zhang J, Kuklin NA, Abbondanzo SJ, Niu XD, Chen SC, Manfra DJ, Wiekowski MT, Sullivan LM, Smith SR, Greenberg HB, Narula SK, Lipp M, Lira SA (2000) CCR6 mediates dendritic cell localization, lymphocyte homeostasis, and immune responses in mucosal tissue. Immunity 12:495–503. doi:10.1016/S1074-7613(00)80201-0
  Article CAS PubMed Google Scholar
• Lugering A, Floer M, Westphal S, Maaser C, Spahn TW, Schmidt MA, Domschke W, Williams IR, Kucharzik T (2005) Absence of CCR6 inhibits CD4+ regulatory T-cell development and M-cell formation inside Peyer's patches. Am J Pathol 166:1647–1654
  PubMed Google Scholar
• Cheng H, Leblond CP (1974) Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. V. Unitarian Theory of the origin of the four epithelial cell types. Am J Anat 141:537–561. doi:10.1002/aja.1001410407
  Article CAS PubMed Google Scholar
• Kerneis S, Bogdanova A, Kraehenbuhl JP, Pringault E (1997) Conversion by Peyer's patch lymphocytes of human enterocytes into M cells that transport bacteria. Science 277:949–952. doi:10.1126/science.277.5328.949
  Article CAS PubMed Google Scholar
• El Bahi S, Caliot E, Bens M, Bogdanova A, Kerneis S, Kahn A, Vandewalle A, Pringault E (2002) Lymphoepithelial interactions trigger specific regulation of gene expression in the M cell-containing follicle-associated epithelium of Peyer's patches. J Immunol 168:3713–3720
  CAS PubMed Google Scholar
• Tyrer P, Ruth Foxwell A, Kyd J, Harvey M, Sizer P, Cripps A (2002) Validation and quantitation of an in vitro M-cell model. Biochem Biophys Res Commun 299:377–383. doi:10.1016/S0006-291X(02)02631-1
  Article CAS PubMed Google Scholar
• Blanco LP, DiRita VJ (2006) Bacterial-associated cholera toxin and GM1 binding are required for transcytosis of classical biotype Vibrio cholerae through an in vitro M cell model system. Cell Microbiol 8:982–998. doi:10.1111/j.1462-5822.2005.00681.x
  Article CAS PubMed Google Scholar
• Golovkina TV, Shlomchik M, Hannum L, Chervonsky A (1999) Organogenic role of B lymphocytes in mucosal immunity. Science 286:1965–1968. doi:10.1126/science.286.5446.1965
  Article CAS PubMed Google Scholar
• Debard N, Sierro F, Browning J, Kraehenbuhl JP (2001) Effect of mature lymphocytes and lymphotoxin on the development of the follicle-associated epithelium and M cells in mouse Peyer's patches. Gastroenterology 120:1173–1182. doi:10.1053/gast.2001.22476
  Article CAS PubMed Google Scholar
• Adachi S, Yoshida H, Kataoka H, Nishikawa S (1997) Three distinctive steps in Peyer's patch formation of murine embryo. Int Immunol 9:507–514. doi:10.1093/intimm/9.4.507
  Article CAS PubMed Google Scholar
• Sharma R, Schumacher U, Adam E (1998) Lectin histochemistry reveals the appearance of M-cells in Peyer's patches of SCID mice after syngeneic normal bone marrow transplantation. J Histochem Cytochem 46:143–148
  CAS PubMed Google Scholar
• Lelouard H, Sahuquet A, Reggio H, Montcourrier P (2001) Rabbit M cells and dome enterocytes are distinct cell lineages. J Cell Sci 114:2077–2083
  CAS PubMed Google Scholar
• Jang MH, Kweon MN, Iwatani K, Yamamoto M, Terahara K, Sasakawa C, Suzuki T, Nochi T, Yokota Y, Rennert PD, Hiroi T, Tamagawa H, Iijima H, Kunisawa J, Yuki Y, Kiyono H (2004) Intestinal villous M cells: an antigen entry site in the mucosal epithelium. Proc Natl Acad Sci U S A 101:6110–6115. doi:10.1073/pnas.0400969101
  Article CAS PubMed Google Scholar
• Niess JH, Brand S, Gu X, Landsman L, Jung S, McCormick BA, Vyas JM, Boes M, Ploegh HL, Fox JG, Littman DR, Reinecker HC (2005) CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307:254–258. doi:10.1126/science.1102901
  Article CAS PubMed Google Scholar
• Rescigno M, Urbano M, Valzasina B, Francolini M, Rotta G, Bonasio R, Granucci F, Kraehenbuhl JP, Ricciardi-Castagnoli P (2001) Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2:361–367. doi:10.1038/86373
  Article CAS PubMed Google Scholar
• Taylor RT, Lugering A, Newell KA, Williams IR (2004) Intestinal cryptopatch formation in mice requires lymphotoxin alpha and the lymphotoxin beta receptor. J Immunol 173:7183–7189
  CAS PubMed Google Scholar
• Allen CD, Cyster JG (2008) Follicular dendritic cell networks of primary follicles and germinal centers: phenotype and function. Semin Immunol 20:14–25. doi:10.1016/j.smim.2007.12.001
  Article CAS PubMed Google Scholar
• Katakai T, Hara T, Lee JH, Gonda H, Sugai M, Shimizu A (2004) A novel reticular stromal structure in lymph node cortex: an immuno-platform for interactions among dendritic cells, T cells and B cells. Int Immunol 16:1133–1142. doi:10.1093/intimm/dxh113
  Article CAS PubMed Google Scholar
• Katakai T, Hara T, Sugai M, Gonda H, Shimizu A (2004) Lymph node fibroblastic reticular cells construct the stromal reticulum via contact with lymphocytes. J Exp Med 200:783–795. doi:10.1084/jem.20040254
  Article CAS PubMed Google Scholar
• Link A, Vogt TK, Favre S, Britschgi MR, Acha-Orbea H, Hinz B, Cyster JG, Luther SA (2007) Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells. Nat Immunol 8:1255–1265. doi:10.1038/ni1513
  Article CAS PubMed Google Scholar
• Gretz JE, Anderson AO, Shaw S (1997) Cords, channels, corridors and conduits: critical architectural elements facilitating cell interactions in the lymph node cortex. Immunol Rev 156:11–24. doi:10.1111/j.1600-065X.1997.tb00955.x
  Article CAS PubMed Google Scholar
• Gretz JE, Kaldjian EP, Anderson AO, Shaw S (1996) Sophisticated strategies for information encounter in the lymph node: the reticular network as a conduit of soluble information and a highway for cell traffic. J Immunol 157:495–499
  CAS PubMed Google Scholar
• Sixt M, Kanazawa N, Selg M, Samson T, Roos G, Reinhardt DP, Pabst R, Lutz MB, Sorokin L (2005) The conduit system transports soluble antigens from the afferent lymph to resident dendritic cells in the T cell area of the lymph node. Immunity 22:19–29. doi:10.1016/j.immuni.2004.11.013
  Article CAS PubMed Google Scholar
• Bajenoff M, Egen JG, Koo LY, Laugier JP, Brau F, Glaichenhaus N, Germain RN (2006) Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes. Immunity 25:989–1001. doi:10.1016/j.immuni.2006.10.011
  Article CAS PubMed Google Scholar
• Cyster JG (1999) Chemokines and cell migration in secondary lymphoid organs. Science 286:2098–2102. doi:10.1126/science.286.5447.2098
  Article CAS PubMed Google Scholar
• Carlsen HS, Haraldsen G, Brandtzaeg P, Baekkevold ES (2005) Disparate lymphoid chemokine expression in mice and men: no evidence of CCL21 synthesis by human high endothelial venules. Blood 106:444–446. doi:10.1182/blood-2004-11-4353
  Article CAS PubMed Google Scholar
• Baekkevold ES, Yamanaka T, Palframan RT, Carlsen HS, Reinholt FP, von Andrian UH, Brandtzaeg P, Haraldsen G (2001) The CCR7 ligand elc (CCL19) is transcytosed in high endothelial venules and mediates T cell recruitment. J Exp Med 193:1105–1112. doi:10.1084/jem.193.9.1105
  Article CAS PubMed Google Scholar
• Lee JW, Epardaud M, Sun J, Becker JE, Cheng AC, Yonekura AR, Heath JK, Turley SJ (2007) Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self. Nat Immunol 8:181–190. doi:10.1038/ni1427
  Article CAS PubMed Google Scholar
• Svensson M, Maroof A, Ato M, Kaye PM (2004) Stromal cells direct local differentiation of regulatory dendritic cells. Immunity 21:805–816. doi:10.1016/j.immuni.2004.10.012
  Article CAS PubMed Google Scholar
• Hammerschmidt SI, Ahrendt M, Bode U, Wahl B, Kremmer E, Forster R, Pabst O (2008) Stromal mesenteric lymph node cells are essential for the generation of gut-homing T cells in vivo. J Exp Med 205:2483–2490. doi:10.1084/jem.20080039
  Article CAS PubMed Google Scholar
• Okuda M, Togawa A, Wada H, Nishikawa S (2007) Distinct activities of stromal cells involved in the organogenesis of lymph nodes and Peyer's patches. J Immunol 179:804–811
  CAS PubMed Google Scholar
• Katakai T, Suto H, Sugai M, Gonda H, Togawa A, Suematsu S, Ebisuno Y, Katagiri K, Kinashi T, Shimizu A (2008) Organizer-like reticular stromal cell layer common to adult secondary lymphoid organs. J Immunol 181:6189–6200
  CAS PubMed Google Scholar
• Miyawaki S, Nakamura Y, Suzuka H, Koba M, Yasumizu R, Ikehara S, Shibata Y (1994) A new mutation, aly, that induces a generalized lack of lymph nodes accompanied by immunodeficiency in mice. Eur J Immunol 24:429–434. doi:10.1002/eji.1830240224
  Article CAS PubMed Google Scholar
• Matsumoto M, Iwamasa K, Rennert PD, Yamada T, Suzuki R, Matsushima A, Okabe M, Fujita S, Yokoyama M (1999) Involvement of distinct cellular compartments in the abnormal lymphoid organogenesis in lymphotoxin-alpha-deficient mice and alymphoplasia (aly) mice defined by the chimeric analysis. J Immunol 163:1584–1591
  CAS PubMed Google Scholar
• Shinkura R, Kitada K, Matsuda F, Tashiro K, Ikuta K, Suzuki M, Kogishi K, Serikawa T, Honjo T (1999) Alymphoplasia is caused by a point mutation in the mouse gene encoding Nf-kappa b-inducing kinase. Nat Genet 22:74–77. doi:10.1038/8780
  Article CAS PubMed Google Scholar
• De Togni P, Goellner J, Ruddle NH, Streeter PR, Fick A, Mariathasan S, Smith SC, Carlson R, Shornick LP, Strauss-Schoenberger J (1994) Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science 264:703–707. doi:10.1126/science.8171322
  Article PubMed Google Scholar
• Yin L, Wu L, Wesche H, Arthur CD, White JM, Goeddel DV, Schreiber RD (2001) Defective lymphotoxin-beta receptor-induced NF-kappaB transcriptional activity in NIK-deficient mice. Science 291:2162–2165. doi:10.1126/science.1058453
  Article CAS PubMed Google Scholar
• Futterer A, Mink K, Luz A, Kosco-Vilbois MH, Pfeffer K (1998) The lymphotoxin beta receptor controls organogenesis and affinity maturation in peripheral lymphoid tissues. Immunity 9:59–70. doi:10.1016/S1074-7613(00)80588-9
  Article CAS PubMed Google Scholar
• Rennert PD, Browning JL, Mebius R, Mackay F, Hochman PS (1996) Surface lymphotoxin alpha/beta complex is required for the development of peripheral lymphoid organs. J Exp Med 184:1999–2006. doi:10.1084/jem.184.5.1999
  Article CAS PubMed Google Scholar
• Adachi S, Yoshida H, Honda K, Maki K, Saijo K, Ikuta K, Saito T, Nishikawa S (1998) Essential role of IL-7 receptor alpha in the formation of Peyer's patch anlage. Int Immunol 10:1–6. doi:10.1093/intimm/10.1.1
  Article CAS PubMed Google Scholar
• Yoshida H, Honda K, Shinkura R, Adachi S, Nishikawa S, Maki K, Ikuta K, Nishikawa SI (1999) IL-7 receptor alpha+ CD3(−) cells in the embryonic intestine induces the organizing center of Peyer's patches. Int Immunol 11:643–655. doi:10.1093/intimm/11.5.643
  Article CAS PubMed Google Scholar
• Hashi H, Yoshida H, Honda K, Fraser S, Kubo H, Awane M, Takabayashi A, Nakano H, Yamaoka Y, Nishikawa S (2001) Compartmentalization of Peyer's patch anlagen before lymphocyte entry. J Immunol 166:3702–3709
  CAS PubMed Google Scholar
• Honda K, Nakano H, Yoshida H, Nishikawa S, Rennert P, Ikuta K, Tamechika M, Yamaguchi K, Fukumoto T, Chiba T, Nishikawa SI (2001) Molecular basis for hematopoietic/mesenchymal interaction during initiation of Peyer's patch organogenesis. J Exp Med 193:621–630. doi:10.1084/jem.193.5.621
  Article CAS PubMed Google Scholar
• Eberl G, Marmon S, Sunshine MJ, Rennert PD, Choi Y, Littman DR (2004) An essential function for the nuclear receptor RORgamma(t) in the generation of fetal lymphoid tissue inducer cells. Nat Immunol 5:64–73. doi:10.1038/ni1022
  Article CAS PubMed Google Scholar
• Rossi SW, Kim MY, Leibbrandt A, Parnell SM, Jenkinson WE, Glanville SH, McConnell FM, Scott HS, Penninger JM, Jenkinson EJ, Lane PJ, Anderson G (2007) RANK signals from CD4(+) 3(−) inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla. J Exp Med 204:1267–1272. doi:10.1084/jem.20062497
  Article CAS PubMed Google Scholar
• Kim MY, Rossi S, Withers D, McConnell F, Toellner KM, Gaspal F, Jenkinson E, Anderson G, Lane PJ (2008) Heterogeneity of lymphoid tissue inducer cell populations present in embryonic and adult mouse lymphoid tissues. Immunology 124:166–174
  Article CAS PubMed Google Scholar
• Mebius RE, Rennert P, Weissman IL (1997) Developing lymph nodes collect CD4+CD3− LTbeta+ cells that can differentiate to APC, NK cells, and follicular cells but not T or B cells. Immunity 7:493–504. doi:10.1016/S1074-7613(00)80371-4
  Article CAS PubMed Google Scholar
• Finke D, Acha-Orbea H, Mattis A, Lipp M, Kraehenbuhl J (2002) CD4+CD3− cells induce Peyer's patch development: role of alpha4beta1 integrin activation by CXCR5. Immunity 17:363–373. doi:10.1016/S1074-7613(02)00395-3
  Article CAS PubMed Google Scholar
• Dejardin E, Droin NM, Delhase M, Haas E, Cao Y, Makris C, Li ZW, Karin M, Ware CF, Green DR (2002) The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways. Immunity 17:525–535. doi:10.1016/S1074-7613(02)00423-5
  Article CAS PubMed Google Scholar
• Hehlgans T, Pfeffer K (2005) The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games. Immunology 115:1–20. doi:10.1111/j.1365-2567.2005.02143.x
  Article CAS PubMed Google Scholar
• Weih F, Caamano J (2003) Regulation of secondary lymphoid organ development by the nuclear factor-kappaB signal transduction pathway. Immunol Rev 195:91–105. doi:10.1034/j.1600-065X.2003.00064.x
  Article CAS PubMed Google Scholar
• Browning JL, Allaire N, Ngam-Ek A, Notidis E, Hunt J, Perrin S, Fava RA (2005) Lymphotoxin-beta receptor signaling is required for the homeostatic control of HEV differentiation and function. Immunity 23:539–550. doi:10.1016/j.immuni.2005.10.002
  Article CAS PubMed Google Scholar
• Furtado GC, Marinkovic T, Martin AP, Garin A, Hoch B, Hubner W, Chen BK, Genden E, Skobe M, Lira SA (2007) Lymphotoxin beta receptor signaling is required for inflammatory lymphangiogenesis in the thyroid. Proc Natl Acad Sci U S A 104:5026–5031. doi:10.1073/pnas.0606697104
  Article CAS PubMed Google Scholar
• Liao S, Ruddle NH (2006) Synchrony of high endothelial venules and lymphatic vessels revealed by immunization. J Immunol 177:3369–3379
  CAS PubMed Google Scholar
• Rumbo M, Sierro F, Debard N, Kraehenbuhl JP, Finke D (2004) Lymphotoxin beta receptor signaling induces the chemokine CCL20 in intestinal epithelium. Gastroenterology 127:213–223. doi:10.1053/j.gastro.2004.04.018
  Article CAS PubMed Google Scholar
• Rennert PD, James D, Mackay F, Browning JL, Hochman PS (1998) Lymph node genesis is induced by signaling through the lymphotoxin beta receptor. Immunity 9:71–79. doi:10.1016/S1074-7613(00)80589-0
  Article CAS PubMed Google Scholar
• Kuprash DV, Tumanov AV, Liepinsh DJ, Koroleva EP, Drutskaya MS, Kruglov AA, Shakhov AN, Southon E, Murphy WJ, Tessarollo L, Grivennikov SI, Nedospasov SA (2005) Novel tumor necrosis factor-knockout mice that lack Peyer's patches. Eur J Immunol 35:1592–1600. doi:10.1002/eji.200526119
  Article CAS PubMed Google Scholar
• Pfeffer K, Matsuyama T, Kundig TM, Wakeham A, Kishihara K, Shahinian A, Wiegmann K, Ohashi PS, Kronke M, Mak TW (1993) Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell 73:457–467. doi:10.1016/0092-8674(93)90134-C
  Article CAS PubMed Google Scholar
• Koni PA, Flavell RA (1998) A role for tumor necrosis factor receptor type 1 in gut-associated lymphoid tissue development: genetic evidence of synergism with lymphotoxin beta. J Exp Med 187:1977–1983. doi:10.1084/jem.187.12.1977
  Article CAS PubMed Google Scholar
• Yoshida H, Naito A, Inoue J, Satoh M, Santee-Cooper SM, Ware CF, Togawa A, Nishikawa S (2002) Different cytokines induce surface lymphotoxin-alphabeta on IL-7 receptor-alpha cells that differentially engender lymph nodes and Peyer's patches. Immunity 17:823–833. doi:10.1016/S1074-7613(02)00479-X
  Article CAS PubMed Google Scholar
• Mold JE, Michaelsson J, Burt TD, Muench MO, Beckerman KP, Busch MP, Lee TH, Nixon DF, McCune JM (2008) Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero. Science 322:1562–1565. doi:10.1126/science.1164511
  Article CAS PubMed Google Scholar
• Finke D, Meier D (2006) Molecular networks orchestrating GALT development. CTMI 308:19–57
  CAS Google Scholar
• Sitnicka E, Brakebusch C, Martensson IL, Svensson M, Agace WW, Sigvardsson M, Buza-Vidas N, Bryder D, Cilio CM, Ahlenius H, Maraskovsky E, Peschon JJ, Jacobsen SE (2003) Complementary signaling through flt3 and interleukin-7 receptor alpha is indispensable for fetal and adult B cell genesis. J Exp Med 198:1495–1506. doi:10.1084/jem.20031152
  Article CAS PubMed Google Scholar
• Cao X, Shores EW, Hu-Li J, Anver MR, Kelsall BL, Russell SM, Drago J, Noguchi M, Grinberg A, Bloom ET et al (1995) Defective lymphoid development in mice lacking expression of the common cytokine receptor gamma chain. Immunity 2:223–238. doi:10.1016/1074-7613(95)90047-0
  Article CAS PubMed Google Scholar
• Kang J, Der S (2004) Cytokine functions in the formative stages of a lymphocyte's life. Curr Opin Immunol 16:180–190. doi:10.1016/j.coi.2004.02.002
  Article CAS PubMed Google Scholar
• Luther SA, Ansel KM, Cyster JG (2003) Overlapping roles of CXCL13, interleukin 7 receptor α, and CCR7 ligands in lymph node development. J Exp Med 197:1191–1198. doi:10.1084/jem.20021294
  Article CAS PubMed Google Scholar
• Park SY, Saijo K, Takahashi T, Osawa M, Arase H, Hirayama N, Miyake K, Nakauchi H, Shirasawa T, Saito T (1995) Developmental defects of lymphoid cells in Jak3 kinase-deficient mice. Immunity 3:771–782. doi:10.1016/1074-7613(95)90066-7
  Article CAS PubMed Google Scholar
• Pandey A, Ozaki K, Baumann H, Levin SD, Puel A, Farr AG, Ziegler SF, Leonard WJ, Lodish HF (2000) Cloning of a receptor subunit required for signaling by thymic stromal lymphopoietin. Nat Immunol 1:59–64. doi:10.1038/76923
  Article CAS PubMed Google Scholar
• Park LS, Martin U, Garka K, Gliniak B, Di Santo JP, Muller W, Largaespada DA, Copeland NG, Jenkins NA, Farr AG, Ziegler SF, Morrissey PJ, Paxton R, Sims JE (2000) Cloning of the murine thymic stromal lymphopoietin (TSLP) receptor: formation of a functional heteromeric complex requires interleukin 7 receptor. J Exp Med 192:659–670. doi:10.1084/jem.192.5.659
  Article CAS PubMed Google Scholar
• Al-Shami A, Spolski R, Kelly J, Fry T, Schwartzberg PL, Pandey A, Mackall CL, Leonard WJ (2004) A role for thymic stromal lymphopoietin in CD4(+) T cell development. J Exp Med 200:159–168. doi:10.1084/jem.20031975
  Article CAS PubMed Google Scholar
• Forster R, Schubel A, Breitfeld D, Kremmer E, Renner-Muller I, Wolf E, Lipp M (1999) CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell 99:23–33. doi:10.1016/S0092-8674(00)80059-8
  Article CAS PubMed Google Scholar
• Nakano H, Mori S, Yonekawa H, Nariuchi H, Matsuzawa A, Kakiuchi T (1998) A novel mutant gene involved in T-lymphocyte-specific homing into peripheral lymphoid organs on mouse chromosome 4. Blood 91:2886–2895
  CAS PubMed Google Scholar
• Ohl L, Henning G, Krautwald S, Lipp M, Hardtke S, Bernhardt G, Pabst O, Förster R (2003) Cooperative mechanisms of CXCR5 and CCR7 in development and organization of secondary lymphoid organs. J Exp Med 197:1199–1204. doi:10.1084/jem.20030169
  Article CAS PubMed Google Scholar
• Metcalf D (1993) Hematopoietic regulators: redundancy or subtlety? Blood 82:3515–3523
  CAS PubMed Google Scholar
• Meier D, Bornmann C, Chappaz S, Schmutz S, Otten LA, Ceredig R, Acha-Orbea H, Finke D (2007) Ectopic lymphoid-organ development occurs through interleukin 7-mediated enhanced survival of lymphoid-tissue-inducer cells. Immunity 26:643–654. doi:10.1016/j.immuni.2007.04.009
  Article CAS PubMed Google Scholar
• Kondo S (2002) The reaction-diffusion system: a mechanism for autonomous pattern formation in the animal skin. Genes Cells 7:535–541. doi:10.1046/j.1365-2443.2002.00543.x
  Article CAS PubMed Google Scholar
• Croker BA, Kiu H, Nicholson SE (2008) SOCS regulation of the JAK/STAT signalling pathway. Semin Cell Dev Biol 19:414–422. doi:10.1016/j.semcdb.2008.07.010
  Article CAS PubMed Google Scholar
• Fernandez-Botran R, Chilton PM, Ma Y (1996) Soluble cytokine receptors: their roles in immunoregulation, disease, and therapy. Adv Immunol 63:269–336. doi:10.1016/S0065-2776(08)60858-5
  Article CAS PubMed Google Scholar
• Veiga-Fernandes H, Coles MC, Foster KE, Patel A, Williams A, Natarajan D, Barlow A, Pachnis V, Kioussis D (2007) Tyrosine kinase receptor RET is a key regulator of Peyer's patch organogenesis. Nature 446:547–551. doi:10.1038/nature05597
  Article CAS PubMed Google Scholar
• Sun Z, Unutmaz D, Zou YR, Sunshine MJ, Pierani A, Brenner-Morton S, Mebius RE, Littman DR (2000) Requirement for RORgamma in thymocyte survival and lymphoid organ development. Science 288:2369–2373. doi:10.1126/science.288.5475.2369
  Article CAS PubMed Google Scholar
• Yokota Y, Mansouri A, Mori S, Sugawara S, Adachi S, Nishikawa S, Gruss P (1999) Development of peripheral lymphoid organs and natural killer cells depends on the helix-loop-helix inhibitor Id2. Nature 397:702–706. doi:10.1038/17812
  Article CAS PubMed Google Scholar
• Kurebayashi S, Ueda E, Sakaue M, Patel DD, Medvedev A, Zhang F, Jetten AM (2000) Retinoid-related orphan receptor gamma (RORgamma) is essential for lymphoid organogenesis and controls apoptosis during thymopoiesis. Proc Natl Acad Sci U S A 97:10132–10137. doi:10.1073/pnas.97.18.10132
  Article CAS PubMed Google Scholar
• Boos MD, Yokota Y, Eberl G, Kee BL (2007) Mature natural killer cell and lymphoid tissue-inducing cell development requires Id2-mediated suppression of E protein activity. J Exp Med 204:1119–1130. doi:10.1084/jem.20061959
  Article CAS PubMed Google Scholar
• Yoshida H, Kawamoto H, Santee S, Hashi H, Honda K, Nishikawa S, Ware C, Katsura Y, Nishikawa S (2001) Expression of alpha(4) beta(7) integrin defines a distinct pathway of lymphoid progenitors committed to T cells, fetal intestinal lymphotoxin producer, NK, and dendritic cells. J Immunol 167:2511–2521
  CAS PubMed Google Scholar
• Mebius RE, Miyamoto T, Christensen J, Domen J, Cupedo T, Weissman IL, Akashi K (2001) The fetal liver counterpart of adult common lymphoid progenitors gives rise to all lymphoid lineages, CD45+CD4+CD3− cells, as well as macrophages. J Immunol 166:6593–6601
  CAS PubMed Google Scholar
• Murray AM, Simm B, Beagley KW (1998) Cytokine gene expression in murine fetal intestine: potential for extrathymic T cell development. Cytokine 10:337–345. doi:10.1006/cyto.1997.0302
  Article CAS PubMed Google Scholar
• Cupedo T, Crellin NK, Papazian N, Rombouts EJ, Weijer K, Grogan JL, Fibbe WE, Cornelissen JJ, Spits H (2009) Human fetal lymphoid tissue-inducer cells are interleukin 17-producing precursors to RORC+ CD127+ natural killer-like cells. Nat Immunol 10:66–74. doi:10.1038/ni.1668
  Article CAS PubMed Google Scholar
• Luci C, Reynders A, Ivanov II, Cognet C, Chiche L, Chasson L, Hardwigsen J, Anguiano E, Banchereau J, Chaussabel D, Dalod M, Littman DR, Vivier E, Tomasello E (2009) Influence of the transcription factor RORgammat on the development of NKp46+ cell populations in gut and skin. Nat Immunol 10:75–82. doi:10.1038/ni.1681
  Article CAS PubMed Google Scholar
• Cella M, Fuchs A, Vermi W, Facchetti F, Otero K, Lennerz JK, Doherty JM, Mills JC, Colonna M (2009) A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature 457:722–725. doi:10.1038/nature07537
  Article CAS PubMed Google Scholar
• Sanos SL, Bui VL, Mortha A, Oberle K, Heners C, Johner C, Diefenbach A (2009) RORgammat and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells. Nat Immunol 10:83–91. doi:10.1038/ni.1684
  Article CAS PubMed Google Scholar
• Satoh-Takayama N, Vosshenrich CA, Lesjean-Pottier S, Sawa S, Lochner M, Rattis F, Mention JJ, Thiam K, Cerf-Bensussan N, Mandelboim O, Eberl G, Di Santo JP (2008) Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity 29:958–970. doi:10.1016/j.immuni.2008.11.001
  Article CAS PubMed Google Scholar
• Takatori H, Kanno Y, Watford WT, Tato CM, Weiss G, Ivanov II, Littman DR, O'Shea JJ (2008) Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22. J Exp Med 206:35–41
  Article PubMed CAS Google Scholar
• Chinen H, Matsuoka K, Sato T, Kamada N, Okamoto S, Hisamatsu T, Kobayashi T, Hasegawa H, Sugita A, Kinjo F, Fujita J, Hibi T (2007) Lamina propria c-kit+ immune precursors reside in human adult intestine and differentiate into natural killer cells. Gastroenterology 133:559–573. doi:10.1053/j.gastro.2007.05.017
  Article CAS PubMed Google Scholar
• Yokota Y, Mori S, Nishikawa SI, Mansouri A, Gruss P, Kusunoki T, Katakai T, Shimizu A (2000) The helix-loop-helix inhibitor Id2 and cell differentiation control. Curr Top Microbiol Immunol 251:35–41
  CAS PubMed Google Scholar
• Eberl G, Littman DR (2004) Thymic origin of intestinal αβ T cells revealed by fate mapping of RORγt+ cells. Science 305:248–251. doi:10.1126/science.1096472
  Article CAS PubMed Google Scholar
• Kim MY, Gaspal FM, Wiggett HE, McConnell FM, Gulbranson-Judge A, Raykundalia C, Walker LS, Goodall MD, Lane PJ (2003) CD4(+) CD3(−) accessory cells costimulate primed CD4 T cells through OX40 and CD30 at sites where T cells collaborate with B cells. Immunity 18:643–654. doi:10.1016/S1074-7613(03)00110-9
  Article CAS PubMed Google Scholar
• Kim MY, Toellner KM, White A, McConnell FM, Gaspal FM, Parnell SM, Jenkinson E, Anderson G, Lane PJ (2006) Neonatal and adult CD4+ CD3− cells share similar gene expression profile, and neonatal cells up-regulate OX40 ligand in response to TL1A (TNFSF15). J Immunol 177:3074–3081
  CAS PubMed Google Scholar
• Kim MY, Anderson G, White A, Jenkinson E, Arlt W, Martensson IL, Erlandsson L, Lane PJ (2005) OX40 ligand and CD30 ligand are expressed on adult but not neonatal CD4+CD3− inducer cells: evidence that IL-7 signals regulate CD30 ligand but not OX40 ligand expression. J Immunol 174:6686–6691
  CAS PubMed Google Scholar
• Lane PJ, Gaspal FM, Kim MY (2005) Two sides of a cellular coin: CD4(+) CD3− cells regulate memory responses and lymph-node organization. Nat Rev Immunol 5:655–660. doi:10.1038/nri1665
  Article CAS PubMed Google Scholar
• Sawa Y, Arima Y, Ogura H, Kitabayashi C, Jiang JJ, Fukushima T, Kamimura D, Hirano T, Murakami M (2009) Hepatic interleukin-7 expression regulates T cell responses. Immunity 30:447–457. doi:10.1016/j.immuni.2009.01.007
  Article CAS PubMed Google Scholar
• Scandella E, Bolinger B, Lattmann E, Miller S, Favre S, Littman DR, Finke D, Luther SA, Junt T, Ludewig B (2008) Restoration of lymphoid organ integrity through the interaction of lymphoid tissue-inducer cells with stroma of the T cell zone. Nat Immunol 9:667–675. doi:10.1038/ni.1605
  Article CAS PubMed Google Scholar
• Ettinger R, Browning JL, Michie SA, van Ewijk W, McDevitt HO (1996) Disrupted splenic architecture, but normal lymph node development in mice expressing a soluble lymphotoxin-beta receptor-IgG1 fusion protein. Proc Natl Acad Sci U S A 93:13102–13107. doi:10.1073/pnas.93.23.13102
  Article CAS PubMed Google Scholar
• Rennert PD, Browning JL, Hochman PS (1997) Selective disruption of lymphotoxin ligands reveals a novel set of mucosal lymph nodes and unique effects on lymph node cellular organization. Int Immunol 9:1627–1639. doi:10.1093/intimm/9.11.1627
  Article CAS PubMed Google Scholar
• Gonzalez M, Mackay F, Browning JL, Kosco-Vilbois MH, Noelle RJ (1998) The sequential role of lymphotoxin and B cells in the development of splenic follicles. J Exp Med 187:997–1007. doi:10.1084/jem.187.7.997
  Article CAS PubMed Google Scholar
• Tumanov AV, Kuprash DV, Mach JA, Nedospasov SA, Chervonsky AV (2004) Lymphotoxin and TNF produced by B cells are dispensable for maintenance of the follicle-associated epithelium but are required for development of lymphoid follicles in the Peyer's patches. J Immunol 173:86–91
  CAS PubMed Google Scholar
• Ware CF, VanArsdale TL, Crowe PD, Browning JL (1995) The ligands and receptors of the lymphotoxin system. Curr Top Microbiol Immunol 198:175–218
  CAS PubMed Google Scholar
• Mackay F, Browning JL (1998) Turning off follicular dendritic cells. Nature 395:26–27. doi:10.1038/25630
  Article CAS PubMed Google Scholar
• Smith MW, James PS, Tivey DR (1987) M cell numbers increase after transfer of SPF mice to a normal animal house environment. Am J Pathol 128:385–389
  CAS PubMed Google Scholar
• Karapetian O, Shakhov AN, Kraehenbuhl JP, Acha-Orbea H (1994) Retroviral infection of neonatal Peyer's patch lymphocytes: the mouse mammary tumor virus model. J Exp Med 180:1511–1516. doi:10.1084/jem.180.4.1511
  Article CAS PubMed Google Scholar
• Bevilacqua G, Marchetti A, Biondi R (1989) Ultrastructural features of the intestinal absorption of mouse mammary tumor virus in newborn BALB/cfRIII mice. Gastroenterology 96:139–145
  CAS PubMed Google Scholar
• Hainaut P, Francois C, Calberg-Bacq CM, Vaira D, Osterrieth PM (1983) Peroral infection of suckling mice with milk-borne mouse mammary tumour virus: uptake of the main viral antigens by the gut. J Gen Virol 64(Pt 12):2535–2548. doi:10.1099/0022-1317-64-12-2535
  Article PubMed Google Scholar
• Acha-Orbea H, Finke D, Attinger A, Schmid S, Wehrli N, Vacheron S, Xenarios I, Scarpellino L, Toellner KM, MacLennan IC, Luther SA (1999) Interplays between mouse mammary tumor virus and the cellular and humoral immune response. Immunol Rev 168:287–303. doi:10.1111/j.1600-065X.1999.tb01299.x
  Article CAS PubMed Google Scholar
• Girardin SE, Boneca IG, Carneiro LA, Antignac A, Jehanno M, Viala J, Tedin K, Taha MK, Labigne A, Zahringer U, Coyle AJ, DiStefano PS, Bertin J, Sansonetti PJ, Philpott DJ (2003) Nod1 detects a unique muropeptide from gram-negative bacterial peptidoglycan. Science 300:1584–1587. doi:10.1126/science.1084677
  Article CAS PubMed Google Scholar
• Fagarasan S, Muramatsu M, Suzuki K, Nagaoka H, Hiai H, Honjo T (2002) Critical roles of activation-induced cytidine deaminase in the homeostasis of gut flora. Science 298:1424–1427. doi:10.1126/science.1077336
  Article CAS PubMed Google Scholar
• Hamann A, Andrew DP, Jablonski-Westrich D, Holzmann B, Butcher EC (1994) Role of alpha 4-integrins in lymphocyte homing to mucosal tissues in vivo. J Immunol 152:3282–3293
  CAS PubMed Google Scholar
• Wagner N, Lohler J, Kunkel EJ, Ley K, Leung E, Krissansen G, Rajewsky K, Muller W (1996) Critical role for beta7 integrins in formation of the gut-associated lymphoid tissue. Nature 382:366–370. doi:10.1038/382366a0
  Article CAS PubMed Google Scholar
• Wang C, McDonough JS, McDonald KG, Huang C, Newberry RD (2008) Alpha4beta7/MAdCAM-1 interactions play an essential role in transitioning cryptopatches into isolated lymphoid follicles and a nonessential role in cryptopatch formation. J Immunol 181:4052–4061
  CAS PubMed Google Scholar
• Velaga S, Herbrand H, Friedrichsen M, Jiong T, Dorsch M, Hoffmann MW, Forster R, Pabst O (2009) Chemokine receptor CXCR5 supports solitary intestinal lymphoid tissue formation, B cell homing, and induction of intestinal IgA responses. J Immunol 182:2610–2619. doi:10.4049/jimmunol.0801141
  Article CAS PubMed Google Scholar
• McDonald KG, McDonough JS, Wang C, Kucharzik T, Williams IR, Newberry RD (2007) CC chemokine receptor 6 expression by B lymphocytes is essential for the development of isolated lymphoid follicles. Am J Pathol 170:1229–1240. doi:10.2353/ajpath.2007.060817
  Article CAS PubMed Google Scholar
• Bals R, Wang X, Meegalla RL, Wattler S, Weiner DJ, Nehls MC, Wilson JM (1999) Mouse beta-defensin 3 is an inducible antimicrobial peptide expressed in the epithelia of multiple organs. Infect Immun 67:3542–3547
  CAS PubMed Google Scholar
• Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, Anderson M, Schroder JM, Wang JM, Howard OM, Oppenheim JJ (1999) Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 286:525–528. doi:10.1126/science.286.5439.525
  Article CAS PubMed Google Scholar
• Newberry RD, McDonough JS, McDonald KG, Lorenz RG (2002) Postgestational lymphotoxin/lymphotoxin beta receptor interactions are essential for the presence of intestinal B lymphocytes. J Immunol 168:4988–4997
  CAS PubMed Google Scholar
• Yamamoto M, Kweon MN, Rennert PD, Hiroi T, Fujihashi K, McGhee JR, Kiyono H (2004) Role of gut-associated lymphoreticular tissues in antigen-specific intestinal IgA immunity. J Immunol 173:762–769
  CAS PubMed Google Scholar
• Mazmanian SK, Round JL, Kasper DL (2008) A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453:620–625. doi:10.1038/nature07008
  Article CAS PubMed Google Scholar
• Ohman L, Franzen L, Rudolph U, Birnbaumer L, Hornquist EH (2002) Regression of Peyer's patches in G alpha i2 deficient mice prior to colitis is associated with reduced expression of Bcl-2 and increased apoptosis. Gut 51:392–397. doi:10.1136/gut.51.3.392
  Article CAS PubMed Google Scholar
• Rudolph U, Finegold MJ, Rich SS, Harriman GR, Srinivasan Y, Brabet P, Boulay G, Bradley A, Birnbaumer L (1995) Ulcerative colitis and adenocarcinoma of the colon in G alpha i2-deficient mice. Nat Genet 10:143–150. doi:10.1038/ng0695-143
  Article CAS PubMed Google Scholar
• Wang Y, Zhang HX, Sun YP, Liu ZX, Liu XS, Wang L, Lu SY, Kong H, Liu QL, Li XH, Lu ZY, Chen SJ, Chen Z, Bao SS, Dai W, Wang ZG (2007) Rig-I−/− mice develop colitis associated with downregulation of G alpha i2. Cell Res 17:858–868. doi:10.1038/cr.2007.81
  Article CAS PubMed Google Scholar
• Spahn TW, Herbst H, Rennert PD, Lugering N, Maaser C, Kraft M, Fontana A, Weiner HL, Domschke W, Kucharzik T (2002) Induction of colitis in mice deficient of Peyer's patches and mesenteric lymph nodes is associated with increased disease severity and formation of colonic lymphoid patches. Am J Pathol 161:2273–2282
  PubMed Google Scholar
• Mackay F, Browning JL, Lawton P, Shah SA, Comiskey M, Bhan AK, Mizoguchi E, Terhorst C, Simpson SJ (1998) Both the lymphotoxin and tumor necrosis factor pathways are involved in experimental murine models of colitis. Gastroenterology 115:1464–1475. doi:10.1016/S0016-5085(98)70025-3
  Article CAS PubMed Google Scholar
• Dohi T, Rennert PD, Fujihashi K, Kiyono H, Shirai Y, Kawamura YI, Browning JL, McGhee JR (2001) Elimination of colonic patches with lymphotoxin beta receptor-Ig prevents Th2 cell-type colitis. J Immunol 167:2781–2790
  CAS PubMed Google Scholar
• Gommerman JL, Browning JL (2003) Lymphotoxin/light, lymphoid microenvironments and autoimmune disease. Nat Rev Immunol 3:642–655. doi:10.1038/nri1151
  Article CAS PubMed Google Scholar
• Kaiserling E (2001) Newly-formed lymph nodes in the submucosa in chronic inflammatory bowel disease. Lymphology 34:22–29
  CAS PubMed Google Scholar
• Connor EM, Eppihimer MJ, Morise Z, Granger DN, Grisham MB (1999) Expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in acute and chronic inflammation. J Leukoc Biol 65:349–355
  CAS PubMed Google Scholar
• Feagan BG, Greenberg GR, Wild G, Fedorak RN, Pare P, McDonald JW, Dube R, Cohen A, Steinhart AH, Landau S, Aguzzi RA, Fox IH, Vandervoort MK (2005) Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin. N Engl J Med 352:2499–2507. doi:10.1056/NEJMoa042982
  Article CAS PubMed Google Scholar
• van Assche G, Rutgeerts P (2002) Antiadhesion molecule therapy in inflammatory bowel disease. Inflamm Bowel Dis 8:291–300. doi:10.1097/00054725-200207000-00009
  Article PubMed Google Scholar
• Carlsen HS, Baekkevold ES, Johansen FE, Haraldsen G, Brandtzaeg P (2002) B cell attracting chemokine 1 (CXCL13) and its receptor CXCR5 are expressed in normal and aberrant gut associated lymphoid tissue. Gut 51:364–371. doi:10.1136/gut.51.3.364
  Article CAS PubMed Google Scholar
• Luther SA, Lopez T, Bai W, Hanahan D, Cyster JG (2000) BLC expression in pancreatic islets causes B cell recruitment and lymphotoxin-dependent lymphoid neogenesis. Immunity 12:471–481. doi:10.1016/S1074-7613(00)80199-5
  Article CAS PubMed Google Scholar
• Ahern PP, Izcue A, Maloy KJ, Powrie F (2008) The interleukin-23 axis in intestinal inflammation. Immunol Rev 226:147–159. doi:10.1111/j.1600-065X.2008.00705.x
  Article PubMed Google Scholar
• Mora JR, Bono MR, Manjunath N, Weninger W, Cavanagh LL, Rosemblatt M, Von Andrian UH (2003) Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells. Nature 424:88–93. doi:10.1038/nature01726
  Article CAS PubMed Google Scholar
• Mucida D, Park Y, Kim G, Turovskaya O, Scott I, Kronenberg M, Cheroutre H (2007) Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 317:256–260. doi:10.1126/science.1145697
  Article CAS PubMed Google Scholar
• Rimoldi M, Chieppa M, Salucci V, Avogadri F, Sonzogni A, Sampietro GM, Nespoli A, Viale G, Allavena P, Rescigno M (2005) Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells. Nat Immunol 6:507–514. doi:10.1038/ni1192
  Article CAS PubMed Google Scholar
• Taylor BC, Zaph C, Troy AE, Du Y, Guild KJ, Comeau MR, Artis D (2009) TSLP regulates intestinal immunity and inflammation in mouse models of helminth infection and colitis. J Exp Med 206:655–667. doi:10.1084/jem.20081499
  Article CAS PubMed Google Scholar
• Kato A, Favoreto S Jr, Avila PC, Schleimer RP (2007) TLR3- and Th2 cytokine-dependent production of thymic stromal lymphopoietin in human airway epithelial cells. J Immunol 179:1080–1087
  CAS PubMed Google Scholar
• Lee HC, Ziegler SF (2007) Inducible expression of the proallergic cytokine thymic stromal lymphopoietin in airway epithelial cells is controlled by NFkappaB. Proc Natl Acad Sci U S A 104:914–919. doi:10.1073/pnas.0607305104
  Article CAS PubMed Google Scholar
• Klimpel GR, Chopra AK, Langley KE, Wypych J, Annable CA, Kaiserlian D, Ernst PB, Peterson JW (1995) A role for stem cell factor and c-kit in the murine intestinal tract secretory response to cholera toxin. J Exp Med 182:1931–1942. doi:10.1084/jem.182.6.1931
  Article CAS PubMed Google Scholar
• Watanabe M, Ueno Y, Yajima T, Iwao Y, Tsuchiya M, Ishikawa H, Aiso S, Hibi T, Ishii H (1995) Interleukin 7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes. J Clin Invest 95:2945–2953. doi:10.1172/JCI118002
  Article CAS PubMed Google Scholar
• Watanabe M, Ueno Y, Yajima T, Okamoto S, Hayashi T, Yamazaki M, Iwao Y, Ishii H, Habu S, Uehira M, Nishimoto H, Ishikawa H, Hata J, Hibi T (1998) Interleukin 7 transgenic mice develop chronic colitis with decreased interleukin 7 protein accumulation in the colonic mucosa. J Exp Med 187:389–402. doi:10.1084/jem.187.3.389
  Article CAS PubMed Google Scholar
• Totsuka T, Kanai T, Nemoto Y, Makita S, Okamoto R, Tsuchiya K, Watanabe M (2007) IL-7 Is essential for the development and the persistence of chronic colitis. J Immunol 178:4737–4748
  CAS PubMed Google Scholar
• Tomita T, Kanai T, Nemoto Y, Totsuka T, Okamoto R, Tsuchiya K, Sakamoto N, Watanabe M (2008) Systemic, but not intestinal, IL-7 is essential for the persistence of chronic colitis. J Immunol 180:383–390
  CAS PubMed Google Scholar