Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells (original) (raw)

• Banchereau, J. & Steinman, R. M. Dendritic cells and the control of immunity. Nature 392, 245–252 (1998).
  Article CAS PubMed Google Scholar
• Valladeau, J. et al. Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. Immunity 12, 71–81 (2000). This paper was the first to identify langerin on the surface of human LCs and to show that langerin induces the formation of Birbeck granules.
  Article CAS PubMed Google Scholar
• Turville, S. G. et al. Diversity of receptors binding HIV on dendritic cell subsets. Nature Immunol. 3, 975–983 (2002).
  Article CAS Google Scholar
• de Witte, L. et al. Langerin is a natural barrier to HIV-1 transmission by Langerhans cells. Nature Med. 13, 367–371 (2007). This study reveals that langerin leads to HIV-1 degradation.
  Article CAS PubMed Google Scholar
• Ginhoux, F. et al. Blood-derived dermal langerin+ dendritic cells survey the skin in the steady state. J. Exp. Med. 204, 3133–3146 (2007). Together with references 6 and 7, this paper reports the presence of langerin+ DCs in the skin that develop and function independently of LCs.
  Article CAS PubMed PubMed Central Google Scholar
• Poulin, L. F. et al. The dermis contains langerin+ dendritic cells that develop and function independently of epidermal Langerhans cells. J. Exp. Med. 204, 3119–3131 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Bursch, L. S. et al. Identification of a novel population of Langerin+ dendritic cells. J. Exp. Med. 204, 3147–3156 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Wang, L. et al. Langerin expressing cells promote skin immune responses under defined conditions. J. Immunol. 180, 4722–4727 (2008).
  Article CAS PubMed Google Scholar
• Ginhoux, F. et al. Langerhans cells arise from monocytes in vivo. Nature Immunol. 7, 265–273 (2006). The first demonstration that LCs are absent in Mcsfr −/− mice and that monocytes repopulate LCs in inflamed skin in vivo in mice.
  Article CAS Google Scholar
• Langerhans, P. Uber die Nerven der menschlichen Haut. Virchows. Arch. Pathol. 44, 325–337 (1868). In this paper, entitled “On the nerves of the human skin”, Paul Langerhans reported for the first time the presence of large cells with long dendrites in the epidermis of human skin.
  Article Google Scholar
• Stingl, G., Tamaki, K. & Katz, S. I. Origin and function of epidermal Langerhans cells. Immunol. Rev. 53, 149–174 (1980).
  Article CAS PubMed Google Scholar
• Schuler, G. et al. Murine epidermal Langerhans cells as a model to study tissue dendritic cells. Adv. Exp. Med. Biol. 329, 243–249 (1993).
  Article CAS PubMed Google Scholar
• Valladeau, J. & Saeland, S. Cutaneous dendritic cells. Semin. Immunol. 17, 273–283 (2005).
  Article CAS PubMed Google Scholar
• Tigelaar, R. E., Lewis, J. M. & Bergstresser, P. R. TCR γ/δ+ dendritic epidermal T cells as constituents of skin-associated lymphoid tissue. J. Invest. Dermatol. 94, 58S–63S (1990).
  Article CAS PubMed Google Scholar
• Birbeck, M. D., Breathnach, A. S. & Everall, J. D. An electron microscope study of basal melanocytes and high-level clear cells (langerhans cells) in vitiligo. J. Invest. Dermatol. 37, 51 (1961). This is the first description of the presence of the conspiscuous Birbeck granules in Langerhans cells.
  Article Google Scholar
• Wolff, K. The fine structure of the Langerhans cell granule. J. Cell Biol. 35, 468–473 (1967).
  Article CAS PubMed PubMed Central Google Scholar
• Tang, A., Amagai, M., Granger, L. G., Stanley, J. R. & Udey, M. C. Adhesion of epidermal Langerhans cells to keratinocytes mediated by E-cadherin. Nature 361, 82–85 (1993).
  Article CAS PubMed Google Scholar
• Cepek, K. L. et al. Adhesion between epithelial cells and T lymphocytes mediated by E-cadherin and the αEβ7 integrin. Nature 372, 190–193 (1994). This study reports for the first time that the integrin CD103 (also known as α E -integrin, part of the α E b 7 -integrin heterodimer) expressed on the cell surface of T cells can bind the adhesion molecule E-cadherin on epithelial cells.
  Article CAS PubMed Google Scholar
• Borkowski, T. A., Letterio, J. J., Farr, A. G. & Udey, M. C. A role for endogenous transforming growth factor β1 in Langerhans cell biology: the skin of transforming growth factor β1 null mice is devoid of epidermal Langerhans cells. J. Exp. Med. 184, 2417–2422 (1996). This study is the first demonstration that TGFβ1 is crucial for LC development in vivo.
  Article CAS PubMed PubMed Central Google Scholar
• Inaba, K. et al. Tissue distribution of the DEC-205 protein that is detected by the monoclonal antibody NLDC-145. I. Expression on dendritic cells and other subsets of mouse leukocytes. Cell. Immunol. 163, 148–156 (1995).
  Article CAS PubMed Google Scholar
• Jiang, W. et al. The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing. Nature 375, 151–155 (1995).
  Article CAS PubMed Google Scholar
• Fithian, E. et al. Reactivity of Langerhans cells with hybridoma antibody. Proc. Natl Acad. Sci. USA 78, 2541–2544 (1981).
  Article CAS PubMed PubMed Central Google Scholar
• Hunger, R. E. et al. Langerhans cells utilize CD1a and langerin to efficiently present nonpeptide antigens to T cells. J. Clin. Invest. 113, 701–708 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Ronger-Savle, S. et al. TGFβ inhibits CD1d expression on dendritic cells. J. Invest. Dermatol. 124, 116–118 (2005).
  Article CAS PubMed Google Scholar
• Mc Dermott, R. et al. Birbeck granules are subdomains of endosomal recycling compartment in human epidermal Langerhans cells, which form where langerin accumulates. Mol. Biol. Cell 13, 317–335 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Valladeau, J. et al. Identification of mouse langerin/CD207 in Langerhans cells and some dendritic cells of lymphoid tissues. J. Immunol. 168, 782–792 (2002).
  Article CAS PubMed Google Scholar
• Takahara, K. et al. Identification and expression of mouse Langerin (CD207) in dendritic cells. Int. Immunol. 14, 433–444 (2002).
  Article CAS PubMed Google Scholar
• Kissenpfennig, A. et al. Disruption of the langerin/CD207 gene abolishes Birbeck granules without a marked loss of Langerhans cell function. Mol. Cell Biol. 25, 88–99 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Verdijk, P. et al. A lack of Birbeck granules in Langerhans cells is associated with a naturally occurring point mutation in the human Langerin gene. J. Invest. Dermatol. 124, 714–717 (2005).
  Article CAS PubMed Google Scholar
• Kelly, R. H., Balfour, B. M., Armstrong, J. A. & Griffiths, S. Functional anatomy of lymph nodes. II. Peripheral lymph-borne mononuclear cells. Anat. Rec. 190, 5–21 (1978). This is one of the first studies to show the presence of veiled (dendritic) cells in lymphatic vessels.
  Article CAS PubMed Google Scholar
• Drexhage, H. A., Mullink, H., de Groot, J., Clarke, J. & Balfour, B. M. A study of cells present in peripheral lymph of pigs with special reference to a type of cell resembling the Langerhans cell. Cell Tissue Res. 202, 407–430 (1979).
  Article CAS PubMed Google Scholar
• Hemmi, H. et al. Skin antigens in the steady state are trafficked to regional lymph nodes by transforming growth factor-β-dependent cells. Int. Immunol. 13, 695–704 (2001).
  Article CAS PubMed Google Scholar
• Stoitzner, P., Tripp, C. H., Douillard, P., Saeland, S. & Romani, N. Migratory Langerhans cells in mouse lymph nodes in steady state and inflammation. J. Invest. Dermatol. 125, 116–125 (2005).
  Article CAS PubMed Google Scholar
• Macatonia, S. E., Knight, S. C., Edwards, A. J., Griffiths, S. & Fryer, P. Localization of antigen on lymph node dendritic cells after exposure to the contact sensitizer fluorescein isothiocyanate. Functional and morphological studies. J. Exp. Med. 166, 1654–1667 (1987).
  Article CAS PubMed Google Scholar
• Randolph, G. J., Ochando, J. & Partida-Sanchez, S. Migration of dendritic cell subsets and their precursors. Annu. Rev. Immunol. 26, 293–316 (2008).
  Article CAS PubMed Google Scholar
• Larsen, C. P. et al. Migration and maturation of Langerhans cells in skin transplants and explants. J. Exp. Med. 172, 1483–1493 (1990).
  Article CAS PubMed Google Scholar
• Pierre, P. et al. Developmental regulation of MHC class II transport in mouse dendritic cells. Nature 388, 787–792 (1997).
  Article CAS PubMed Google Scholar
• Ruedl, C., Koebel, P., Bachmann, M., Hess, M. & Karjalainen, K. Anatomical origin of dendritic cells determines their life span in peripheral lymph nodes. J. Immunol. 165, 4910–4916 (2000).
  Article CAS PubMed Google Scholar
• Ohl, L. et al. CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions. Immunity 21, 279–288 (2004). This is the first paper to identify the crucial role of CCR7 in skin-DC migration to the draining lymph nodes.
  Article CAS PubMed Google Scholar
• Jakob, T., Ring, J. & Udey, M. C. Multistep navigation of Langerhans/dendritic cells in and out of the skin. J. Allergy Clin. Immunol. 108, 688–696 (2001).
  Article CAS PubMed Google Scholar
• Inaba, K. et al. High levels of a major histocompatibility complex II–self peptide complex on dendritic cells from the T cell areas of lymph nodes. J. Exp. Med. 186, 665–672 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Katz, S. I., Tamaki, K. & Sachs, D. H. Epidermal Langerhans cells are derived from cells originating in bone marrow. Nature 282, 324–326 (1979).
  Article CAS PubMed Google Scholar
• Frelinger, J. G., Hood, L., Hill, S. & Frelinger, J. A. Mouse epidermal Ia molecules have a bone marrow origin. Nature 282, 321–323 (1979). References 42 and 43 were the two first studies to show the haematopoietic origin of LCs.
  Article CAS PubMed Google Scholar
• Merad, M. et al. Langerhans cells renew in the skin throughout life under steady-state conditions. Nature Immunol. 3, 1135–1141 (2002). This is the first paper to describe how LCs replenish in situ in the steady state but are repopulated by blood precursor cells during skin injury. This paper also describes for the first time that LC repopulation in inflamed skin depends on CCR2.
  Article CAS Google Scholar
• Iijima, N., Linehan, M. M., Saeland, S. & Iwasaki, A. Vaginal epithelial dendritic cells renew from bone marrow precursors. Proc. Natl Acad. Sci. USA 104, 19061–19066 (2007).
  Article PubMed PubMed Central Google Scholar
• Holt, P. G., Haining, S., Nelson, D. J. & Sedgwick, J. D. Origin and steady-state turnover of class II MHC-bearing dendritic cells in the epithelium of the conducting airways. J. Immunol. 153, 256–261 (1994).
  CAS PubMed Google Scholar
• Liu, K. et al. Origin of dendritic cells in peripheral lymphoid organs of mice. Nature Immunol. 8, 578–583 (2007). This study shows that DCs cycle in situ in lymphoid organs but are maintained by circulating precursor cells.
  Article CAS Google Scholar
• Merad, M. et al. Depletion of host Langerhans cells before transplantation of donor alloreactive T cells prevents skin graft-versus-host disease. Nature Med. 10, 510–517 (2004).
  Article CAS PubMed Google Scholar
• Vishwanath, M. et al. Development of intravital intermittent confocal imaging system for studying Langerhans cell turnover. J. Invest. Dermatol. 126, 2452–2457 (2006).
  Article CAS PubMed Google Scholar
• Kamath, A. T., Henri, S., Battye, F., Tough, D. F. & Shortman, K. Developmental kinetics and lifespan of dendritic cells in mouse lymphoid organs. Blood 100, 1734–1741 (2002).
  Article CAS PubMed Google Scholar
• Kissenpfennig, A. et al. Dynamics and function of Langerhans cells in vivo: dermal dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells. Immunity 22, 643–654 (2005).
  Article CAS PubMed Google Scholar
• Bennett, C. L. et al. Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity. J. Cell Biol. 169, 569–576 (2005). References 51 and 52 were the first two papers to describe the langerin–DTR mice.
  Article CAS PubMed PubMed Central Google Scholar
• Jung, S. et al. In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens. Immunity 17, 211–220 (2002). This is the first study demonstrating that elimination of DCs in vivo abrogates priming of CD8+ T cells against systemic pathogen infection.
  Article CAS PubMed PubMed Central Google Scholar
• Czernielewski, J., Vaigot, P. & Prunieras, M. Epidermal Langerhans cells — a cycling cell population. J. Invest. Dermatol. 84, 424–426 (1985). The first study to report that LCs cycle in situ.
  Article CAS PubMed Google Scholar
• Czernielewski, J. M. & Demarchez, M. Further evidence for the self-reproducing capacity of Langerhans cells in human skin. J. Invest. Dermatol. 88, 17–20 (1987).
  Article CAS PubMed Google Scholar
• Giacometti, L. & Montagna, W. Langerhans cells: uptake of tritiated thymidine. Science 157, 439–440 (1967).
  Article CAS PubMed Google Scholar
• Krueger, G. G., Daynes, R. A. & Emam, M. Biology of Langerhans cells: selective migration of Langerhans cells into allogeneic and xenogeneic grafts on nude mice. Proc. Natl Acad. Sci. USA 80, 1650–1654 (1983).
  Article CAS PubMed PubMed Central Google Scholar
• Kanitakis, J., Petruzzo, P. & Dubernard, J. M. Turnover of epidermal Langerhans' cells. N. Engl. J. Med. 351, 2661–2662 (2004). A study showing that in one patient that received a limb graft, LCs remained of host origin and were not replaced by blood-derived precursor cells for over 1 year after transplant.
  Article CAS PubMed Google Scholar
• Collin, M. P. et al. The fate of human Langerhans cells in hematopoietic stem cell transplantation. J. Exp. Med. 203, 27–33 (2006). This study shows that, in the absence of graft-versus-host disease, host LCs can remain in the skin despite complete donor-derived chimerism in the blood.
  Article CAS PubMed PubMed Central Google Scholar
• Collin, M. P., Bogunovic, M. & Merad, M. DC homeostasis in hematopoietic stem cell transplantation. Cytotherapy 9, 521–531 (2007).
  Article CAS PubMed Google Scholar
• Miyauchi, S. & Hashimoto, K. Epidermal Langerhans cells undergo mitosis during the early recovery phase after ultraviolet-B irradiation. J. Invest. Dermatol. 88, 703–708 (1987).
  Article CAS PubMed Google Scholar
• Kumamoto, T. et al. Hair follicles serve as local reservoirs of skin mast cell precursors. Blood 102, 1654–1660 (2003). This is the first demonstration that the hair follicle is also a reservoir for the mast-cell precursor.
  Article CAS PubMed Google Scholar
• Blanpain, C. & Fuchs, E. Epidermal stem cells of the skin. Annu. Rev. Cell Dev. Biol. 22, 339–373 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Gilliam, A. C. et al. The human hair follicle: a reservoir of CD40+ B7-deficient Langerhans cells that repopulate epidermis after UVB exposure. J. Invest. Dermatol. 110, 422–427 (1998). This study shows that after exposure to ultraviolet B radiation that depletes epidermal LCs but does not affect the hair follicle, LCs are repopulated from the hair follicle.
  Article CAS PubMed Google Scholar
• Bennett, C. L., Noordegraaf, M., Martina, C. A. & Clausen, B. E. Langerhans cells are required for efficient presentation of topically applied hapten to T cells. J. Immunol. 179, 6830–6835 (2007). This is one of the first demonstrations that LCs are required to initiate T-cell priming against topical antigens.
  Article CAS PubMed Google Scholar
• Kaplan, D. H. et al. Autocrine/paracrine TGFβ1 is required for the development of epidermal Langerhans cells. J. Exp. Med. 204, 2545–2552 (2007). This study shows that autocrine TGFβ1 is required for LC development.
  Article CAS PubMed PubMed Central Google Scholar
• Strobl, H. et al. TGF-β 1 promotes in vitro development of dendritic cells from CD34+ hemopoietic progenitors. J. Immunol. 157, 1499–1507 (1996).
  CAS PubMed Google Scholar
• Geissmann, F. et al. Transforming growth factor β1, in the presence of granulocyte/macrophage colony-stimulating factor and interleukin 4, induces differentiation of human peripheral blood monocytes into dendritic Langerhans cells. J. Exp. Med. 187, 961–966 (1998). This is the first demonstration that human monocytes can differentiate into LCs in vitro.
  Article CAS PubMed PubMed Central Google Scholar
• Hacker, C. et al. Transcriptional profiling identifies Id2 function in dendritic cell development. Nature Immunol. 4, 380–386 (2003). This is the first demonstration that ID2 is required for LC development.
  Article CAS Google Scholar
• Fainaru, O. et al. Runx3 regulates mouse TGF-β-mediated dendritic cell function and its absence results in airway inflammation. EMBO J. 23, 969–979 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Witmer-Pack, M. D. et al. Identification of macrophages and dendritic cells in the osteopetrotic (op/op) mouse. J. Cell Sci. 104, 1021–1029 (1993).
  Article PubMed Google Scholar
• Lin, H. et al. Discovery of a cytokine and its receptor by functional screening of the extracellular proteome. Science 320, 807–811 (2008).
  Article CAS PubMed Google Scholar
• Stanley, E. R. et al. Biology and action of colony-stimulating factor-1. Mol. Reprod. Dev. 46, 4–10 (1997).
  Article CAS PubMed Google Scholar
• Onai, N., Obata-Onai, A., Schmid, M. A. & Manz, M. G. Flt3 in regulation of type-I interferon producing and dendritic cell development. Ann. NY Acad. Sci. 1106, 253–261 (2007).
  Article CAS PubMed Google Scholar
• Bogunovic, M. et al. Identification of a radio-resistant and cycling dermal dendritic cell population in mice and men. J. Exp. Med. 203, 2627–2638 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Sato, N. et al. CC chemokine receptor (CCR)2 is required for langerhans cell migration and localization of T helper cell type 1 (Th1)-inducing dendritic cells. Absence of CCR2 shifts the _Leishmania major_-resistant phenotype to a susceptible state dominated by Th2 cytokines, B cell outgrowth, and sustained neutrophilic inflammation. J. Exp. Med. 192, 205–218 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Cook, D. N. et al. CCR6 mediates dendritic cell localization, lymphocyte homeostasis, and immune responses in mucosal tissue. Immunity 12, 495–503 (2000).
  Article CAS PubMed Google Scholar
• Vanbervliet, B. et al. Sequential involvement of CCR2 and CCR6 ligands for immature dendritic cell recruitment: possible role at inflamed epithelial surfaces. Eur. J. Immunol. 32, 231–242 (2002).
  Article CAS PubMed Google Scholar
• Larregina, A. T. et al. Dermal-resident CD14+ cells differentiate into Langerhans cells. Nature Immunol. 2, 1151–1158 (2001).
  Article CAS Google Scholar
• Schaerli, P., Willimann, K., Ebert, L. M., Walz, A. & Moser, B. Cutaneous CXCL14 targets. Blood precursors to epidermal niches for Langerhans cell differentiation. Immunity 23, 331–342 (2005).
  Article CAS PubMed Google Scholar
• Reis e Sousa, C. Dendritic cells in a mature stage. Nature Rev. Immunol. 6, 476–483 (2006).
  Article CAS Google Scholar
• Jiang, A. et al. Disruption of E-cadherin-mediated adhesion induces a functionally distinct pathway of dendritic cellmaturation. Immunity 27, 610–624 (2007). This is the first paper to describe an alternative DC-maturation pathway that leads to the upregulation of CCR7 without inducing cytokine release and is thought to have a key role in the induction of tolerance.
  Article PubMed PubMed Central CAS Google Scholar
• Banchereau, J. et al. Immunobiology of dendritic cells. Annu. Rev. Immunol. 18, 767–811 (2000).
  Article CAS PubMed Google Scholar
• Stoitzner, P. et al. Visualization and characterization of migratory Langerhans cells in murine skin and lymph nodes by antibodies against Langerin/CD207. J. Invest. Dermatol. 120, 266–274 (2003).
  Article CAS PubMed Google Scholar
• Geissmann, F. et al. Accumulation of immature Langerhans cells in human lymph nodes draining chronically inflamed skin. J. Exp. Med. 196, 417–430 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Douillard, P. et al. Mouse lymphoid tissue contains distinct subsets of langerin/CD207 dendritic cells, only one of which represents epidermal-derived Langerhans cells. J. Invest. Dermatol. 125, 983–994 (2005).
  Article CAS PubMed Google Scholar
• Cheong, C. et al. Production of monoclonal antibodies that recognize the extracellular domain of mouse langerin/CD207. J. Immunol. Methods 324, 48–62 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Flacher, V. et al. Expression of langerin/CD207 reveals dendritic cell heterogeneity between inbred mouse strains. Immunology 123, 339–347 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Mayer, W. J. et al. Characterization of antigen-presenting cells in fresh and cultured human corneas using novel dendritic cell markers. Invest. Ophthalmol. Vis. Sci. 48, 4459–4467 (2007).
  Article PubMed Google Scholar
• Santoro, A. et al. Recruitment of dendritic cells in oral lichen planus. J. Pathol. 205, 426–434 (2005).
  Article PubMed Google Scholar
• Sung, S. S. et al. A major lung CD103 (αE)-β7 integrin-positive epithelial dendritic cell population expressing Langerin and tight junction proteins. J. Immunol. 176, 2161–2172 (2006).
  Article CAS PubMed Google Scholar
• Johansson-Lindbom, B. et al. Functional specialization of gut CD103+ dendritic cells in the regulation of tissue-selective T cell homing. J. Exp. Med. 202, 1063–1073 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Chikwava, K. & Jaffe, R. Langerin (CD207) staining in normal pediatric tissues, reactive lymph nodes, and childhood histiocytic disorders. Pediatr. Dev. Pathol. 7, 607–614 (2004). This is the first identification of langerin+CD1a+ cells in human tissue other than the skin.
  Article CAS PubMed Google Scholar
• Segerer, S. et al. Compartment specific expression of dendritic cell markers in human glomerulonephritis. Kidney Int. 73, 533–537 (2008). This is the first identification of langerin+CD1a+ cells in human kidneys.
  Article CAS PubMed Google Scholar
• Jaensson, E. et al. Small intestinal CD103+ dendritic cells display unique functional properties that are conserved between mice and humans. J. Exp. Med. 205, 2139–2149 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Kamath, A. T. et al. The development, maturation, and turnover rate of mouse spleen dendritic cell populations. J. Immunol. 165, 6762–6770 (2000).
  Article CAS PubMed Google Scholar
• Fogg, D. K. et al. A clonogenic bone marrow progenitor specific for macrophages and dendritic cells. Science 311, 83–87 (2006).
  Article CAS PubMed Google Scholar
• Massberg, S. et al. Immunosurveillance by hematopoietic progenitor cells trafficking through blood, lymph, and peripheral tissues. Cell 131, 994–1008 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Bonifaz, L. et al. Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+T cell tolerance. J. Exp. Med. 196, 1627–1638 (2002). This is the first demonstration that targeting antigens to DCs in the steady state leads to tolerance.
  Article CAS PubMed PubMed Central Google Scholar
• Dudziak, D. et al. Differential antigen processing by dendritic cell subsets in vivo. Science 315, 107–111 (2007).
  Article CAS PubMed Google Scholar
• Schuler, G. & Steinman, R. M. Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J. Exp. Med. 161, 526–546 (1985). This study was the first to show that Langerhans cells can differentiate in vitro into DCs that can prime naive T cells.
  Article CAS PubMed Google Scholar
• Allan, R. S. et al. Epidermal viral immunity induced by CD8α+ dendritic cells but not by Langerhans cells. Science 301, 1925–1928 (2003). This study shows that LCs are unable to prime CD8+ T cells following epidermal HSV infection.
  Article CAS PubMed Google Scholar
• He, Y., Zhang, J., Donahue, C. & Falo, L. D. Jr. Skin-derived dendritic cells induce potent CD8+ T cell immunity in recombinant lentivector-mediated genetic immunization. Immunity 24, 643–656 (2006). This study shows that migratory skin DCs prime antigen-specific T cells after lentivirus-vector infection of the skin.
  Article CAS PubMed PubMed Central Google Scholar
• Jones, C. A. et al. Herpes simplex virus type 2 induces rapid cell death and functional impairment of murine dendritic cells in vitro. J. Virol. 77, 11139–11149 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Bosnjak, L. et al. Herpes simplex virus infection of human dendritic cells induces apoptosis and allows cross-presentation via uninfected dendritic cells. J. Immunol. 174, 2220–2227 (2005).
  Article CAS PubMed Google Scholar
• Leon, B., Lopez-Bravo, M. & Ardavin, C. Monocyte-derived dendritic cells formed at the infection site control the induction of protective T helper 1 responses against Leishmania. Immunity 26, 519–531 (2007).
  Article CAS PubMed Google Scholar
• Sacks, D. L. Metacyclogenesis in Leishmania promastigotes. Exp. Parasitol. 69, 100–103 (1989).
  Article CAS PubMed Google Scholar
• Belkaid, Y. et al. CD8+ T cells are required for primary immunity in C57BL/6 mice following low-dose, intradermal challenge with Leishmania major. J. Immunol. 168, 3992–4000 (2002).
  Article CAS PubMed Google Scholar
• Klechevsky, E. et al. Functional specializations of human epidermal langerhans cells and CD14+ dermal dendritic cells. Immunity 29, 497–510 (2008). This study shows that human LCs are efficient at cross-presenting antigens to CD8+ T cells and at inducing T H 1-cell responses, whereas dermal DCs are better at priming follicular T-helper cells and inducing B-cell antibody switching.
  Article CAS PubMed PubMed Central Google Scholar
• Ueno, H. et al. Dendritic cell subsets in health and disease. Immunol. Rev. 219, 118–142 (2007).
  Article CAS PubMed Google Scholar
• Stoecklinger, A. et al. Epidermal langerhans cells are dispensable for humoral and cell-mediated immunity elicited by gene gun immunization. J. Immunol. 179, 886–893 (2007).
  Article CAS PubMed Google Scholar
• Stoitzner, P. et al. Tumor immunotherapy by epicutaneous immunization requires langerhans cells. J. Immunol. 180, 1991–1998 (2008). This is the first demonstration that LCs are required for the induction of the antitumour immune response following epidermal vaccination with tumour antigens.
  Article CAS PubMed Google Scholar
• Kaplan, D. H., Jenison, M. C., Saeland, S., Shlomchik, W. D. & Shlomchik, M. J. Epidermal langerhans cell-deficient mice develop enhanced contact hypersensitivity. Immunity 23, 611–620 (2005).
  Article CAS PubMed Google Scholar
• Steinman, R. M., Hawiger, D. & Nussenzweig, M. C. Tolerogenic dendritic cells. Annu. Rev. Immunol. 21, 685–711 (2003).
  Article CAS PubMed Google Scholar
• Waithman, J. et al. Skin-derived dendritic cells can mediate deletional tolerance of class I-restricted self-reactive T cells. J. Immunol. 179, 4535–4541 (2007).
  Article CAS PubMed Google Scholar
• Loser, K. et al. Epidermal RANKL controls regulatory T-cell numbers via activation of dendritic cells. Nature Med. 12, 1372–1379 (2006).
  Article CAS PubMed Google Scholar
• Mehling, A. et al. Overexpression of CD40 ligand in murine epidermis results in chronic skin inflammation and systemic autoimmunity. J. Exp. Med. 194, 615–628 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• GeurtsvanKessel, C. H. et al. Clearance of influenza virus from the lung depends on migratory langerin+CD11b− but not plasmacytoid dendritic cells. J. Exp. Med. 205, 1621–1634 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Belz, G. T. et al. Distinct migrating and nonmigrating dendritic cell populations are involved in MHC class I-restricted antigen presentation after lung infection with virus. Proc. Natl Acad. Sci. USA 101, 8670–8675 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• del Rio, M. L., Rodriguez-Barbosa, J. I., Kremmer, E. & Forster, R. CD103− and CD103+ bronchial lymph node dendritic cells are specialized in presenting and cross-presenting innocuous antigen to CD4+ and CD8+ T cells. J. Immunol. 178, 6861–6866 (2007).
  Article CAS PubMed Google Scholar
• Coppes-Zantinga, A. & Egeler, R. M. The Langerhans cell histiocytosis X files revealed. Br. J. Haematol. 116, 3–9 (2002).
  Article PubMed Google Scholar
• Nezelof, C., Basset, F. & Rousseau, M. F. Histiocytosis X histogenetic arguments for a Langerhans cell origin. Biomedicine 18, 365–371 (1973).
  CAS PubMed Google Scholar
• Geissmann, F. et al. Differentiation of Langerhans cells in Langerhans cell histiocytosis. Blood 97, 1241–1248 (2001).
  Article CAS PubMed Google Scholar
• Emile, J. F., Fraitag, S., Leborgne, M., de Prost, Y. & Brousse, N. In situ expression of activation markers by Langerhans' cells containing GM-CSF. Adv. Exp. Med. Biol. 378, 101–103 (1995).
  Article CAS PubMed Google Scholar
• Nezelof, C. & Basset, F. An hypothesis Langerhans cell histiocytosis: the failure of the immune system to switch from an innate to an adaptive mode. Pediatr. Blood Cancer 42, 398–400 (2004). This is the first study showing that cells in histiocytosis X lesions contain Birbeck granules, which suggests their potential LC origin, and proposed that the term histiocytosis X should be replaced with the term Langerhans-cell histiocytosis.
  Article PubMed Google Scholar
• Yu, R. C., Chu, C., Buluwela, L. & Chu, A. C. Clonal proliferation of Langerhans cells in Langerhans cell histiocytosis. Lancet 343, 767–768 (1994).
  Article CAS PubMed Google Scholar
• Willman, C. L. et al. Langerhans'-cell histiocytosis (histiocytosis X) — a clonal proliferative disease. N. Engl. J. Med. 331, 154–160 (1994).
  Article CAS PubMed Google Scholar
• Senechal, B. et al. Expansion of regulatory T cells in patients with Langerhans cell histiocytosis. PLoS Med. 4, e253 (2007).
  Article PubMed PubMed Central CAS Google Scholar
• Schouten, B. et al. Expression of cell cycle-related gene products in Langerhans cell histiocytosis. J. Pediatr. Hematol. Oncol. 24, 727–732 (2002).
  Article PubMed Google Scholar
• Savell, V. H. Jr, Sherman, T., Scheuermann, R. H., Siddiqui, A. M. & Margraf, L. R. Bcl-2 expression in Langerhans' cell histiocytosis. Pediatr. Dev. Pathol. 1, 210–215 (1998).
  Article PubMed Google Scholar
• Bjorck, P., Banchereau, J. & Flores-Romo, L. CD40 ligation counteracts Fas-induced apoptosis of human dendritic cells. Int. Immunol. 9, 365–372 (1997).
  Article CAS PubMed Google Scholar
• Wong, B. R. et al. TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor. J. Exp. Med. 186, 2075–2080 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Bechan, G. I., Egeler, R. M. & Arceci, R. J. Biology of Langerhans cells and Langerhans cell histiocytosis. Int. Rev. Cytol. 254, 1–43 (2006).
  Article CAS PubMed Google Scholar
• Steiner, Q. G. et al. In vivo transformation of mouse conventional CD8α+ dendritic cells leads to progressive multisystem histiocytosis. Blood 111, 2073–2082 (2008).
  Article CAS PubMed Google Scholar
• Pileri, S. A. et al. Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases. Histopathology 41, 1–29 (2002).
  Article CAS PubMed Google Scholar
• Figdor, C. G., van Kooyk, Y. & Adema, G. J. C-type lectin receptors on dendritic cells and Langerhans cells. Nature Rev. Immunol. 2, 77–84 (2002).
  Article CAS Google Scholar
• Idoyaga, J. et al. Cutting Edge: Langerin/CD207 receptor on dendritic cells mediates efficient antigen presentation on MHC I and II products in vivo. J. Immunol. 180, 3647–3650 (2008).
  Article CAS PubMed Google Scholar
• Piguet, V. & Steinman, R. M. The interaction of HIV with dendritic cells: outcomes and pathways. Trends Immunol. 28, 503–510 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Hladik, F. & McElrath, M. J. Setting the stage: host invasion by HIV. Nature Rev. Immunol. 8, 447–457 (2008).
  Article CAS Google Scholar
• Fahrbach, K. M. et al. Activated CD34-derived Langerhans cells mediate transinfection with human immunodeficiency virus. J. Virol. 81, 6858–6868 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Riedl, E., Tada, Y. & Udey, M. C. Identification and characterization of an alternatively spliced isoform of mouse Langerin/CD207. J. Invest. Dermatol. 123, 78–86 (2004).
  Article CAS PubMed Google Scholar
• Ward, E. M., Stambach, N. S., Drickamer, K. & Taylor, M. E. Polymorphisms in human langerin affect stability and sugar binding activity. J. Biol. Chem. 281, 15450–15456 (2006).
  Article CAS PubMed Google Scholar
• Boes, M. et al. T-cell engagement of dendritic cells rapidly rearranges MHC class II transport. Nature 418, 983–988 (2002).
  Article CAS PubMed Google Scholar
• Fukuzumi, T. et al. Differences in irradiation susceptibility and turnover between mucosal and connective tissue-type mast cells of mice. Exp. Hematol. 18, 843–847 (1990).
  CAS PubMed Google Scholar
• Matsumoto, Y. & Fujiwara, M. Absence of donor-type major histocompatibility complex class I antigen-bearing microglia in the rat central nervous system of radiation bone marrow chimeras. J. Neuroimmunol. 17, 71–82 (1987).
  Article CAS PubMed Google Scholar
• Berland, R. & Wortis, H. H. Origins and functions of B-1 cells with notes on the role of CD5. Annu. Rev. Immunol. 20, 253–300 (2002).
  Article CAS PubMed Google Scholar
• Merad, M. & Ginhoux, F. Dendritic cell genealogy: a new stem or just another branch? Nature Immunol. 8, 1199–1201 (2007).
  Article CAS Google Scholar
• Takahashi, K. et al. Heterogeneity of dendritic cells in human superficial lymph node: in vitro maturation of immature dendritic cells into mature or activated interdigitating reticulum cells. Am. J. Pathol. 153, 745–755 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Schiavoni, G. et al. ICSBP is critically involved in the normal development and trafficking of Langerhans cells and dermal dendritic cells. Blood 103, 2221–2228 (2004).
  Article CAS PubMed Google Scholar