Triggers and drivers of autoimmunity: lessons from coeliac disease (original) (raw)

• Dicke, W. Coeliac disease. Investigation of the harmful effects of certain types of cereal on patients with coeliac disease. Thesis, Univ. Utrecht (1950).
  Google Scholar
• van Berge-Henegouwen, G. P. & Mulder, C. J. Pioneer in the gluten free diet: Willem-Karel Dicke 1905–1962, over 50 years of gluten free diet. Gut 34, 1473–1475 (1993).
  Article CAS PubMed PubMed Central Google Scholar
• Paulley, J. W. Observation on the aetiology of idiopathic steatorrhoea; jejunal and lymph-node biopsies. Br. Med. J. 2, 1318–1321 (1954).
  Article CAS PubMed PubMed Central Google Scholar
• Green, P. H. & Cellier, C. Celiac disease. N. Engl. J. Med. 357, 1731–1743 (2007).
  Article CAS PubMed Google Scholar
• Dieterich, W. et al. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nature Med. 3, 797–801 (1997).
  Article CAS PubMed Google Scholar
• Sollid, L. M. & Lie, B. A. Celiac disease genetics: current concepts and practical applications. Clin. Gastroenterol. Hepatol. 3, 843–851 (2005).
  Article CAS PubMed Google Scholar
• Trynka, G. et al. Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease. Nature Genet. 43, 1193–1201 (2011).
  Article CAS PubMed Google Scholar
• Smyth, D. J. et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N. Engl. J. Med. 359, 2767–2777 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Zhernakova, A. et al. Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci. PLoS Genet. 7, e1002004 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Trynka, G., Wijmenga, C. & van Heel, D. A. A genetic perspective on coeliac disease. Trends Mol. Med. 16, 537–550 (2010).
  Article CAS PubMed Google Scholar
• Cotsapas, C. et al. Pervasive sharing of genetic effects in autoimmune disease. PLoS Genet. 7, e1002254 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Voight, B. F. & Cotsapas, C. Human genetics offers an emerging picture of common pathways and mechanisms in autoimmunity. Curr. Opin. Immunol. 24, 552–557 (2012).
  Article CAS PubMed Google Scholar
• Maurano, M. T. et al. Systematic localization of common disease-associated variation in regulatory DNA. Science 337, 1190–1195 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Lyons, P. A. et al. Genetically distinct subsets within ANCA-associated vasculitis. N. Engl. J. Med. 367, 214–223 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• van Venrooij, W. J., van Beers, J. J. & Pruijn, G. J. Anti-CCP antibodies: the past, the present and the future. Nature Rev. Rheumatol. 7, 391–398 (2011).
  Article CAS Google Scholar
• Marzari, R. et al. Molecular dissection of the tissue transglutaminase autoantibody response in celiac disease. J. Immunol. 166, 4170–4176 (2001).
  Article CAS PubMed Google Scholar
• Di Niro, R. et al. High abundance of plasma cells secreting transglutaminase 2-specific IgA autoantibodies with limited somatic hypermutation in celiac disease intestinal lesions. Nature Med. 18, 441–445 (2012).
  Article CAS PubMed Google Scholar
• Bjorck, S., Brundin, C., Lorinc, E., Lynch, K. F. & Agardh, D. Screening detects a high proportion of celiac disease in young HLA-genotyped children. J. Pediatr. Gastroenterol. Nutr. 50, 49–53 (2010).
  Article PubMed Google Scholar
• Klareskog, L., Ronnelid, J., Lundberg, K., Padyukov, L. & Alfredsson, L. Immunity to citrullinated proteins in rheumatoid arthritis. Annu. Rev. Immunol. 26, 651–675 (2008).
  Article CAS PubMed Google Scholar
• Sollid, L. M. Molecular basis of celiac disease. Annu. Rev. Immunol. 18, 53–81 (2000).
  Article CAS PubMed Google Scholar
• Turner, J. R. in Robbins and Cotran Pathologic Basis of Disease (eds Kumar, V., Abbas, A. K., Fausto, N. & Aster, J. C.) 763–831 (Elsevier, 2009).
  Google Scholar
• Hüe, S. et al. A direct role for NKG2D/MICA interaction in villous atrophy during celiac disease. Immunity 21, 367–377 (2004).
  Article PubMed Google Scholar
• Meresse, B. et al. Coordinated induction by IL15 of a TCR-independent NKG2D signaling pathway converts CTL into lymphokine-activated killer cells in celiac disease. Immunity 21, 357–366 (2004).
  Article CAS PubMed Google Scholar
• Meresse, B. et al. Reprogramming of CTLs into natural killer-like cells in celiac disease. J. Exp. Med. 203, 1343–1355 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Jabri, B. & Sollid, L. M. Tissue-mediated control of immunopathology in coeliac disease. Nature Rev. Immunol. 9, 858–870 (2009).
  Article CAS Google Scholar
• Groh, V., Bruhl, A., El-Gabalawy, H., Nelson, J. L. & Spies, T. Stimulation of T cell autoreactivity by anomalous expression of NKG2D and its MIC ligands in rheumatoid arthritis. Proc. Natl Acad. Sci. USA 100, 9452–9457 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Ogasawara, K. et al. NKG2D blockade prevents autoimmune diabetes in NOD mice. Immunity 20, 757–767 (2004).
  Article CAS PubMed Google Scholar
• Asquith, D. L. & McInnes, I. B. Emerging cytokine targets in rheumatoid arthritis. Curr. Opin. Rheumatol. 19, 246–251 (2007).
  Article CAS PubMed Google Scholar
• Michalak-Stoma, A. et al. Cytokine network in psoriasis revisited. Eur. Cytokine Netw. 22, 160–168 (2011).
  CAS PubMed Google Scholar
• Rentzos, M. & Rombos, A. The role of IL-15 in central nervous system disorders. Acta Neurol. Scand. 125, 77–82 (2012).
  Article CAS PubMed Google Scholar
• Mention, J. J. et al. Interleukin 15: a key to disrupted intraepithelial lymphocyte homeostasis and lymphomagenesis in celiac disease. Gastroenterology 125, 730–745 (2003).
  Article CAS PubMed Google Scholar
• Tang, F. et al. Cytosolic PLA2 is required for CTL-mediated immunopathology of celiac disease via NKG2D and IL-15. J. Exp. Med. 206, 707–719 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Groh, V. et al. Costimulation of CD8αβ T cells by NKG2D via engagement by MIC induced on virus-infected cells. Nature Immunol. 2, 255–260 (2001).
  Article CAS Google Scholar
• Roberts, A. I. et al. NKG2D receptors induced by IL-15 costimulate CD28-negative effector CTL in the tissue microenvironment. J. Immunol. 167, 5527–5530 (2001).
  Article CAS PubMed Google Scholar
• Sulkanen, S. et al. Tissue transglutaminase autoantibody enzyme-linked immunosorbent assay in detecting celiac disease. Gastroenterology 115, 1322–1328 (1998).
  Article CAS PubMed Google Scholar
• Bardella, M. T. et al. Coeliac disease: a histological follow-up study. Histopathology 50, 465–471 (2007).
  Article CAS PubMed Google Scholar
• Molberg, O. et al. Gliadin specific, HLA DQ2-restricted T cells are commonly found in small intestinal biopsies from coeliac disease patients, but not from controls. Scand. J. Immunol. 46, 103–108 (1997).
  Article CAS PubMed Google Scholar
• Sollid, L. M., Qiao, S. W., Anderson, R. P., Gianfrani, C. & Koning, F. Nomenclature and listing of celiac disease relevant gluten T-cell epitopes restricted by HLA-DQ molecules. Immunogenetics 64, 455–460 (2012).
  Article PubMed PubMed Central Google Scholar
• Lundin, K. E. et al. Gliadin-specific, HLA-DQ(α1*0501, β1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients. J. Exp. Med. 178, 187–196 (1993).
  Article CAS PubMed Google Scholar
• Lundin, K. E., Scott, H., Fausa, O., Thorsby, E. & Sollid, L. M. T cells from the small intestinal mucosa of a DR4, DQ7/DR4, DQ8 celiac disease patient preferentially recognize gliadin when presented by DQ8. Hum. Immunol. 41, 285–291 (1994).
  Article CAS PubMed Google Scholar
• Molberg, O. et al. Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease. Nature Med. 4, 713–717 (1998).
  Article CAS PubMed Google Scholar
• van de Wal, Y. et al. Selective deamidation by tissue transglutaminase strongly enhances gliadin-specific T cell reactivity. J. Immunol. 161, 1585–1588 (1998).
  CAS PubMed Google Scholar
• Tollefsen, S. et al. HLA-DQ2 and -DQ8 signatures of gluten T cell epitopes in celiac disease. J. Clin. Invest. 116, 2226–2236 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Osman, A. A. et al. B cell epitopes of gliadin. Clin. Exp. Immunol. 121, 248–254 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Shan, L. et al. Structural basis for gluten intolerance in celiac sprue. Science 297, 2275–2279 (2002).
  Article CAS PubMed Google Scholar
• Bodd, M. et al. HLA-DQ2-restricted gluten-reactive T cells produce IL-21 but not IL-17 or IL-22. Mucosal Immunol. 3, 594–601 (2010).
  Article CAS PubMed Google Scholar
• Abadie, V., Sollid, L. M., Barreiro, L. B. & Jabri, B. Integration of genetic and immunological insights into a model of celiac disease pathogenesis. Annu. Rev. Immunol. 29, 493–525 (2011).
  Article CAS PubMed Google Scholar
• Sollid, L. M. Coeliac disease: dissecting a complex inflammatory disorder. Nature Rev. Immunol. 2, 647–655 (2002).
  Article CAS Google Scholar
• Mäki, M. in Seventh International Symposium on Coeliac Disease (eds Feighery, C. & O'Farelly, C.) 246–252 (Oak Tree Press, 1992).
  Google Scholar
• Sollid, L. M., Molberg, O., McAdam, S. & Lundin, K. E. Autoantibodies in coeliac disease: tissue transglutaminase—guilt by association? Gut 41, 851–852 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Fleckenstein, B. et al. Molecular characterization of covalent complexes between tissue transglutaminase and gliadin peptides. J. Biol. Chem. 279, 17607–17616 (2004).
  Article CAS PubMed Google Scholar
• Prause, C. et al. Antibodies against deamidated gliadin as new and accurate biomarkers of childhood coeliac disease. J. Pediatr. Gastroenterol. Nutr. 49, 52–58 (2009).
  Article CAS PubMed Google Scholar
• Devendra, D. & Eisenbarth, G. S. Interferon alpha—a potential link in the pathogenesis of viral-induced type 1 diabetes and autoimmunity. Clin. Immunol. 111, 225–233 (2004).
  Article CAS PubMed Google Scholar
• Fujinami, R. S. & Oldstone, M. B. Amino acid homology between the encephalitogenic site of myelin basic protein and virus: mechanism for autoimmunity. Science 230, 1043–1045 (1985).
  Article CAS PubMed Google Scholar
• Wucherpfennig, K. W. & Strominger, J. L. Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell 80, 695–705 (1995).
  Article CAS PubMed PubMed Central Google Scholar
• Lawson, C. M. Evidence for mimicry by viral antigens in animal models of autoimmune disease including myocarditis. Cell. Mol. Life Sci. 57, 552–560 (2000).
  Article CAS PubMed Google Scholar
• Pabst, O. & Mowat, A. M. Oral tolerance to food protein. Mucosal Immunol. 5, 232–239 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• DePaolo, R. W. et al. Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens. Nature 471, 220–224 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Monteleone, G. et al. Role of interferon α in promoting T helper cell type 1 responses in the small intestine in coeliac disease. Gut 48, 425–429 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Raki, M. et al. Plasmacytoid dendritic cells are scarcely represented in the human gut mucosa and are not recruited to the celiac lesion. Mucosal Immunol. 23 Jan 2013 (doi:10.1038/mi.2012.136)
  Article PubMed CAS Google Scholar
• Medzhitov, R. & Janeway, C. A. Jr. Innate immune recognition and control of adaptive immune responses. Semin. Immunol. 10, 351–353 (1998).
  Article CAS PubMed Google Scholar
• Di Sabatino, A. et al. Evidence for the role of interferon-alfa production by dendritic cells in the Th1 response in celiac disease. Gastroenterology 133, 1175–1187 (2007).
  Article CAS PubMed Google Scholar
• Maiuri, L. et al. Association between innate response to gliadin and activation of pathogenic T cells in coeliac disease. Lancet 362, 30–37 (2003).
  Article CAS PubMed Google Scholar
• Barone, M. V. et al. Growth factor-like activity of gliadin, an alimentary protein: implications for coeliac disease. Gut 56, 480–488 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Terrazzano, G. et al. Gliadin regulates the NK–dendritic cell cross-talk by HLA-E surface stabilization. J. Immunol. 179, 372–381 (2007).
  Article CAS PubMed Google Scholar
• Junker, Y. et al. Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4. J. Exp. Med. 209, 2395–2408 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Troncone, R. & Auricchio, S. Rotavirus and celiac disease: clues to the pathogenesis and perspectives on prevention. J. Pediatr. Gastroenterol. Nutr. 44, 527–528 (2007).
  Article PubMed Google Scholar
• Stene, L. C. et al. Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: a longitudinal study. Am. J. Gastroenterol. 101, 2333–2340 (2006).
  Article CAS PubMed Google Scholar
• Hober, D. & Sauter, P. Pathogenesis of type 1 diabetes mellitus: interplay between enterovirus and host. Nature Rev. Endocrinol. 6, 279–289 (2010).
  Article Google Scholar
• Siegel, M. et al. Extracellular transglutaminase 2 is catalytically inactive, but is transiently activated upon tissue injury. PLoS ONE 3, e1861 (2008).
  Article PubMed PubMed Central CAS Google Scholar
• Jun, H. S. & Yoon, J. W. A new look at viruses in type 1 diabetes. Diabetes Metab. Res. Rev. 19, 8–31 (2003).
  Article CAS PubMed Google Scholar
• Rizza, P., Moretti, F. & Belardelli, F. Recent advances on the immunomodulatory effects of IFN-α: implications for cancer immunotherapy and autoimmunity. Autoimmunity 43, 204–209 (2010).
  Article CAS PubMed Google Scholar
• Carrero, J. A., Calderon, B. & Unanue, E. R. Type I interferon sensitizes lymphocytes to apoptosis and reduces resistance to Listeria infection. J. Exp. Med. 200, 535–540 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Woodward, J. J., Iavarone, A. T. & Portnoy, D. A. c-di-AMP secreted by intracellular Listeria monocytogenes activates a host type I interferon response. Science 328, 1703–1705 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Manca, C. et al. Virulence of a Mycobacterium tuberculosis clinical isolate in mice is determined by failure to induce Th1 type immunity and is associated with induction of IFN-α/β. Proc. Natl Acad. Sci. USA 98, 5752–5757 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Jones, J. W. et al. Absent in melanoma 2 is required for innate immune recognition of Francisella tularensis. Proc. Natl Acad. Sci. USA 107, 9771–9776 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Round, J. L. & Mazmanian, S. K. The gut microbiota shapes intestinal immune responses during health and disease. Nature Rev. Immunol. 9, 313–323 (2009).
  Article CAS Google Scholar
• Maynard, C. L., Elson, C. O., Hatton, R. D. & Weaver, C. T. Reciprocal interactions of the intestinal microbiota and immune system. Nature 489, 231–241 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Hooper, L. V., Littman, D. R. & Macpherson, A. J. Interactions between the microbiota and the immune system. Science 336, 1268–1273 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Atkinson, M. A. & Chervonsky, A. Does the gut microbiota have a role in type 1 diabetes? Early evidence from humans and animal models of the disease. Diabetologia 55, 2868–2877 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Mathis, D. & Benoist, C. Microbiota and autoimmune disease: the hosted self. Cell Host Microbe 10, 297–301 (2011).
  Article CAS PubMed Google Scholar
• Forsberg, G. et al. Presence of bacteria and innate immunity of intestinal epithelium in childhood celiac disease. Am. J. Gastroenterol. 99, 894–904 (2004).
  Article PubMed Google Scholar
• Tjellstrom, B. et al. Gut microflora associated characteristics in children with celiac disease. Am. J. Gastroenterol. 100, 2784–2788 (2005).
  Article CAS PubMed Google Scholar
• Sanz, Y. et al. Differences in faecal bacterial communities in coeliac and healthy children as detected by PCR and denaturing gradient gel electrophoresis. FEMS Immunol. Med. Microbiol. 51, 562–568 (2007).
  Article CAS PubMed Google Scholar
• Di Cagno, R. et al. Duodenal and faecal microbiota of celiac children: molecular, phenotype and metabolome characterization. BMC Microbiol. 11, 219 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Nistal, E. et al. Differences of small intestinal bacteria populations in adults and children with/without celiac disease: effect of age, gluten diet, and disease. Inflamm. Bowel Dis. 18, 649–656 (2012).
  Article PubMed Google Scholar
• De Palma, G. et al. Intestinal dysbiosis and reduced immunoglobulin-coated bacteria associated with coeliac disease in children. BMC Microbiol. 10, 63 (2010).
  Article PubMed PubMed Central CAS Google Scholar
• Collado, M. C., Donat, E., Ribes-Koninckx, C., Calabuig, M. & Sanz, Y. Specific duodenal and faecal bacterial groups associated with paediatric coeliac disease. J. Clin. Pathol. 62, 264–269 (2009).
  Article CAS PubMed Google Scholar
• Nadal, I., Donat, E., Ribes-Koninckx, C., Calabuig, M. & Sanz, Y. Imbalance in the composition of the duodenal microbiota of children with coeliac disease. J. Med. Microbiol. 56, 1669–1674 (2007).
  Article CAS PubMed Google Scholar
• Sanchez, E. et al. Reduced diversity and increased virulence-gene carriage in intestinal enterobacteria of coeliac children. BMC Gastroenterol. 8, 50 (2008).
  Article PubMed PubMed Central CAS Google Scholar
• Sanchez, E., Ribes-Koninckx, C., Calabuig, M. & Sanz, Y. Intestinal Staphylococcus spp. and virulent features associated with coeliac disease. J. Clin. Pathol. 65, 830–834 (2012).
  Article CAS PubMed Google Scholar
• Kagnoff, M. F. et al. Evidence for the role of a human intestinal adenovirus in the pathogenesis of coeliac disease. Gut 28, 995–1001 (1987).
  Article CAS PubMed PubMed Central Google Scholar
• Benoist, C. & Mathis, D. Autoimmunity provoked by infection: how good is the case for T cell epitope mimicry? Nature Immunol. 2, 797–801 (2001).
  Article CAS Google Scholar
• Wegner, N. et al. Peptidylarginine deiminase from Porphyromonas gingivalis citrullinates human fibrinogen and α-enolase: implications for autoimmunity in rheumatoid arthritis. Arthritis Rheum. 62, 2662–2672 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Wu, H. J. et al. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32, 815–827 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Saleh, M. & Elson, C. O. Experimental inflammatory bowel disease: insights into the host-microbiota dialog. Immunity 34, 293–302 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Khan, K. J. et al. Antibiotic therapy in inflammatory bowel disease: a systematic review and meta-analysis. Am. J. Gastroenterol. 106, 661–673 (2011).
  Article CAS PubMed Google Scholar
• Janowitz, H. D., Croen, E. C. & Sachar, D. B. The role of the fecal stream in Crohn's disease: an historical and analytic review. Inflamm. Bowel Dis. 4, 29–39 (1998).
  Article CAS PubMed Google Scholar
• Mattner, J. et al. Liver autoimmunity triggered by microbial activation of natural killer T cells. Cell Host Microbe 3, 304–315 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Shewry, R. P., Tatham, A. & Kasarda, D. D. in Coeliac disease (ed. Marsh, M. N.) (Blackwell Scientific Publications, 1992).
  Google Scholar
• Alp, M. H. & Wright, R. Autoantibodies to reticulin in patients with idiopathic steatorrhoea, coeliac disease, and Crohn's disease, and their relation to immunoglobulins and dietary antibodies. Lancet 2, 682–685 (1971).
  Article CAS PubMed Google Scholar
• Seah, P. P., Fry, L., Rossiter, M. A., Hoffbrand, A. V. & Holborow, E. J. Anti-reticulin antibodies in childhood coeliac disease. Lancet 2, 681–682 (1971).
  Article CAS PubMed Google Scholar
• Chorzelski, T. P. et al. IgA anti-endomysium antibody. A new immunological marker of dermatitis herpetiformis and coeliac disease. Br. J. Dermatol. 111, 395–402 (1984).
  Article CAS PubMed Google Scholar
• Ladinser, B., Rossipal, E. & Pittschieler, K. Endomysium antibodies in coeliac disease: an improved method. Gut 35, 776–778 (1994).
  Article CAS PubMed PubMed Central Google Scholar
• Sanchez, D. et al. Occurrence of IgA and IgG autoantibodies to calreticulin in coeliac disease and various autoimmune diseases. J. Autoimmun. 15, 441–449 (2000).
  Article CAS PubMed Google Scholar
• Clemente, M. G. et al. Enterocyte actin autoantibody detection: a new diagnostic tool in celiac disease diagnosis: results of a multicenter study. Am. J. Gastroenterol. 99, 1551–1556 (2004).
  Article CAS PubMed Google Scholar
• Rostom, A. et al. The diagnostic accuracy of serologic tests for celiac disease: a systematic review. Gastroenterology 128, S38–S46 (2005).
  Article PubMed Google Scholar
• Husby, S. et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J. Pediatr. Gastroenterol. Nutr. 54, 136–160 (2012).
  Article CAS PubMed Google Scholar
• Lorand, L. & Graham, R. M. Transglutaminases: crosslinking enzymes with pleiotropic functions. Nature Rev. Mol. Cell. Biol. 4, 140–156 (2003).
  Article CAS Google Scholar
• Piper, J. L., Gray, G. M. & Khosla, C. High selectivity of human tissue transglutaminase for immunoactive gliadin peptides: implications for celiac sprue. Biochemistry 41, 386–393 (2002).
  Article CAS PubMed Google Scholar
• Stamnaes, J., Pinkas, D. M., Fleckenstein, B., Khosla, C. & Sollid, L. M. Redox regulation of transglutaminase 2 activity. J. Biol. Chem. 285, 25402–25409 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Dorum, S. et al. The preferred substrates for transglutaminase 2 in a complex wheat gluten digest are peptide fragments harboring celiac disease T-cell epitopes. PLoS ONE 5, e14056 (2010).
  Article PubMed PubMed Central CAS Google Scholar
• Maslowski, K. M. & Mackay, C. R. Diet, gut microbiota and immune responses. Nature Immunol. 12, 5–9 (2011).
  Article CAS Google Scholar