The pro-Th2 cytokine IL-33 directly interacts with invariant NKT and NK cells to induce IFN-gamma production.
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.
Bourgeois
Elvire
E
CNRS urR 8147, Faculté de Médecine, Université Paris Descartes, Hôpital Necker, Paris, France.
Van
Linh Pham
LP
Samson
Michel
M
Diem
Séverine
S
Barra
Anne
A
Roga
Stéphane
S
Gombert
Jean-Marc
JM
Schneider
Elke
E
Dy
Michel
M
Gourdy
Pierre
P
Girard
Jean-Philippe
JP
Herbelin
André
A
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
C506536:IL33 protein, human; D000067596:Interleukin-33; D007378:Interleukins; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma