title: Langerhans cells regulate cutaneous injury by licensing CD8 effector cells recruited to the skin.
abstract: Langerhans cells (LCs) are a distinct population of dendritic cells that form a contiguous network in the epidermis of the skin. Although LCs possess many of the properties of highly proficient dendritic cells, recent studies have indicated that they are not necessary to initiate cutaneous immunity. In this study, we used a tractable model of cutaneous GVHD, induced by topical application of a Toll-like receptor agonist, to explore the role of LCs in the development of tissue injury. By adapting this model to permit inducible and selective depletion of host LCs, we found that GVHD was significantly reduced when LCs were absent. However, LCs were not required either for CD8 T-cell activation within the draining lymph node or subsequent homing of effector cells to the epidermis. Instead, we found that LCs were necessary for inducing transcription of IFN-γ and other key effector molecules by donor CD8 cells in the epidermis, indicating that they license CD8 cells to induce epithelial injury. These data demonstrate a novel regulatory role for epidermal LCs during the effector phase of an inflammatory immune response in the skin.
authors.affiliation: Transplantation Immunology Group, Department of Haematology, Division of Cancer Studies, University College London, London, United Kingdom. c.bennett@medsch.ucl.ac.uk
authors.forename: Clare L
authors.initials: CL
authors.lastname: Bennett
authors.forename: Farnaz
authors.initials: F
authors.lastname: Fallah-Arani
authors.forename: Thomas
authors.initials: T
authors.lastname: Conlan
authors.forename: Celine
authors.initials: C
authors.lastname: Trouillet
authors.forename: Hugh
authors.initials: H
authors.lastname: Goold
authors.forename: Laurent
authors.initials: L
authors.lastname: Chorro
authors.forename: Barry
authors.initials: B
authors.lastname: Flutter
authors.forename: Terry K
authors.initials: TK
authors.lastname: Means
authors.forename: Frédéric
authors.initials: F
authors.lastname: Geissmann
authors.forename: Ronjon
authors.initials: R
authors.lastname: Chakraverty
mesh_terms: D000634:Aminoquinolines / Q000633:toxicity; D000818:Animals; D002450:Cell Communication; D002478:Cells, Cultured; D002678:Chimera; D003602:Cytotoxicity, Immunologic; D004817:Epidermis / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006086:Graft vs Host Disease / Q000276:immunology; D053804:Granzymes / Q000235:genetics / Q000378:metabolism; D000077271:Imiquimod; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D051193:Toll-Like Receptors / Q000819:agonists; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000634:Aminoquinolines; D012333:RNA, Messenger; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D053804:Granzymes; C509214:Gzmb protein, mouse; D000077271:Imiquimod