title: Invariant NKT cells suppress CD8(+) T-cell-mediated allergic contact dermatitis independently of regulatory CD4(+) T cells.
abstract: Invariant natural killer T (iNKT) cells expressing a CD1d-restricted invariant αβTCR have key regulatory roles in autoimmunity, pathogen immunity, and tumor surveillance, but their function in the control of allergic skin diseases remains poorly documented. Using a model of contact hypersensitivity (CHS) to the hapten DNFB, we show here that iNKT cell deficiency results in enhanced skin inflammation due to augmented hapten-specific IFN-γ-producing CD8(+) effectors in skin draining lymph nodes (dLNs) and their massive recruitment into the allergen-exposed skin. Adoptive transfer and antibody depletion experiments as well as in vitro studies revealed that iNKT cells (1) reduce the severity of CHS, even in presensitized mice, (2) require hapten presentation by CD1d(+) dendritic cells (DCs) to dampen skin inflammation, and (3) produce IL-4 and IL-13 after CD1d-dependent in vitro stimulation by hapten-loaded DCs only in the presence of IFN-γ released from activated CD8(+) effector T cells. In corollary, mice double deficient in IL-4 and IL-13 exhibit an exacerbated CHS. Finally, iNKT-suppressive function is independent of Foxp3(+) regulatory T cells (Tregs). These data highlight that, besides Foxp3(+) Tregs, iNKT cells are potent downregulators of CD8(+) T cell-mediated CHS, and underscore that both cell types are important for the regulation of allergic skin inflammation.
authors.affiliation: Université de Lyon, Lyon, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Goubier
authors.forename: Marc
authors.initials: M
authors.lastname: Vocanson
authors.forename: Claire
authors.initials: C
authors.lastname: Macari
authors.forename: Gaelle
authors.initials: G
authors.lastname: Poyet
authors.forename: André
authors.initials: A
authors.lastname: Herbelin
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Nicolas
authors.forename: Bertrand
authors.initials: B
authors.lastname: Dubois
authors.forename: Dominique
authors.initials: D
authors.lastname: Kaiserlian
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D055610:Antigens, CD1d; D015704:CD4 Antigens; C526879:Cd1d1 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018793:Interleukin-13; D015847:Interleukin-4; D007371:Interferon-gamma