title: The pro-Th2 cytokine IL-33 directly interacts with invariant NKT and NK cells to induce IFN-gamma production.
abstract: IL-33 has recently been identified as a cytokine endowed with pro-Th2 functions, raising the question of its effect on invariant natural killer T cell (iNKT), which are potent IL-4 producers. Here, we report a two-fold increase of iNKT-cell counts in spleen and liver after a 7-day treatment of mice with IL-33, which results from a direct effect, given that purified iNKT cells express the T1/ST2 receptor constitutively and respond to IL-33 by in vitro expansion and functional activation. Conversely to the expected pro-Th2 effect, IL-33 induced a preferential increase in IFN-gamma rather than IL-4 production upon TCR engagement that depended on endogenous IL-12. Moreover, in combination with the pro-inflammatory cytokine IL-12, IL-33 enhanced IFN-gamma production by both iNKT and NK cells. Taken together these data support the conclusion that IL-33 can contribute as a co-stimulatory factor to innate cellular immune responses.
authors.affiliation: CNRS urR 8147, Faculté de Médecine, Université Paris Descartes, Hôpital Necker, Paris, France.
authors.forename: Elvire
authors.initials: E
authors.lastname: Bourgeois
authors.forename: Linh Pham
authors.initials: LP
authors.lastname: Van
authors.forename: Michel
authors.initials: M
authors.lastname: Samson
authors.forename: Séverine
authors.initials: S
authors.lastname: Diem
authors.forename: Anne
authors.initials: A
authors.lastname: Barra
authors.forename: Stéphane
authors.initials: S
authors.lastname: Roga
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Gombert
authors.forename: Elke
authors.initials: E
authors.lastname: Schneider
authors.forename: Michel
authors.initials: M
authors.lastname: Dy
authors.forename: Pierre
authors.initials: P
authors.lastname: Gourdy
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Girard
authors.forename: André
authors.initials: A
authors.lastname: Herbelin
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000819:agonists / Q000276:immunology / Q000378:metabolism*; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism*; D000067596:Interleukin-33; D015847:Interleukin-4 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000276:immunology* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: C506536:IL33 protein, human; D000067596:Interleukin-33; D007378:Interleukins; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma