title: Induced IL-17-producing invariant NKT cells require activation in presence of TGF-β and IL-1β.
abstract: IL-17 production by innate-like lymphocytes, including γδ and invariant NKT (iNKT) cells, have been ascribed to specific lineages that are endowed with this functional specialization during thymic differentiation. IL-17-producing iNKT cells have been described as a CD4(-)NK1.1(-) lineage in mice and CD161(+) in humans. We found that, in mice, noncommitted iNKT cells can be induced to produce IL-17 when activated in presence of TGF-β and IL-1β. This peripheral induction of IL-17 expression could be observed in any subset irrespectively of CD4 and NK1.1 expression, the process leading to loss of NK1.1 expression and partial CD4 downmodulation. Furthermore, induced IL-17-producing iNKT cells were sufficient to drive neutrophilic airways inflammation upon intratracheal adoptive cell transfer into congenic mice. Taken together, our data show that similarly to regulatory T cells, which have a natural and peripherally induced subset, IL-17 production by iNKT cells can also be imprinted in natural iNKT17 cells or peripherally induced.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-025 Lisbon, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Monteiro
authors.forename: Catarina F
authors.initials: CF
authors.lastname: Almeida
authors.forename: Ana
authors.initials: A
authors.lastname: Agua-Doce
authors.forename: Luis
authors.initials: L
authors.lastname: Graca
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis*; D053583:Interleukin-1beta / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D055611:Natural Killer T-Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D039942:Neuropilin-1 / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D012137:Respiratory System / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D020381:Interleukin-17; D053583:Interleukin-1beta; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D039942:Neuropilin-1