title: IL-17A and IL-2-expanded regulatory T cells cooperate to inhibit Th1-mediated rejection of MHC II disparate skin grafts.
abstract: Several evidences suggest that regulatory T cells (Treg) promote Th17 differentiation. Based on this hypothesis, we tested the effect of IL-17A neutralization in a model of skin transplantation in which long-term graft survival depends on a strong in vivo Treg expansion induced by transient exogenous IL-2 administration. As expected, IL-2 supplementation prevented rejection of MHC class II disparate skin allografts but, surprisingly, not in IL-17A-deficient recipients. We attested that IL-17A was not required for IL-2-mediated Treg expansion, intragraft recruitment or suppressive capacities. Instead, IL-17A prevented allograft rejection by inhibiting Th1 alloreactivity independently of Tregs. Indeed, T-bet expression of naive alloreactive CD4+ T cells and the subsequent Th1 immune response was significantly enhanced in IL-17A deficient mice. Our results illustrate for the first time a protective role of IL-17A in CD4+-mediated allograft rejection process.
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Benoît
authors.initials: B
authors.lastname: Vokaer
authors.forename: Louis-Marie
authors.initials: LM
authors.lastname: Charbonnier
authors.forename: Philippe H
authors.initials: PH
authors.lastname: Lemaître
authors.forename: Chloé
authors.initials: C
authors.lastname: Spilleboudt
authors.forename: Alain
authors.initials: A
authors.lastname: Le Moine
mesh_terms: D000818:Animals; D002450:Cell Communication; D049109:Cell Proliferation; D015870:Gene Expression; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000172:deficiency / Q000276:immunology*; D007376:Interleukin-2 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: D000949:Histocompatibility Antigens Class II; D020381:Interleukin-17; D007376:Interleukin-2; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor