A natural protective function of invariant NKT cells in a mouse model of innate-cell-driven lung inflammation.
Activation of invariant natural killer T (iNKT) cells by treatment with their α-galactosyl ceramide ligand provides therapeutic benefits in several immune inflammatory settings. Given the artificial nature of this stimulation, the natural regulatory functions of iNKT remain uncertain. Addressing this issue in a mouse model of innate-cell-driven lung inflammation induced by the cytokine/alarmin IL-33 that targets iNKT cells, we found that eosinophil and neutrophil recruitment was markedly increased in treated iNKT cell-deficient (Jα18 KO) mice, as was the local production of eotaxin and keratinocyte chemoattractant chemokines. By contrast, lung inflammation decreased after adoptive transfer of iNKT cells, which restored the WT inflammatory response in Jα18 KO mice. Finally, we established that this natural anti-inflammatory function of iNKT cells depends on their IFN-γ production and on endogenous IL-12. Our study provides the first evidence of a protective role of iNKT cells during lung inflammation that does not require pharmacological TCR engagement.
INSERM U935, Hôpital Paul Brousse, Université Paris-Sud XI, Villejuif, France.
Elvire A
EA
Bourgeois
Anaïs
A
Levescot
Séverine
S
Diem
Angélique
A
Chauvineau
Hortense
H
Bergès
Pierre
P
Milpied
Agnès
A
Lehuen
Diane
D
Damotte
Jean-Marc
JM
Gombert
Elke
E
Schneider
Jean-Philippe
JP
Girard
Pierre
P
Gourdy
André
A
Herbelin
D019264:Adoptive Transfer; D000818:Animals; D001991:Bronchitis / Q000097:blood / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002452:Cell Count; D018925:Chemokines / Q000097:blood / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D004804:Eosinophils / Q000473:pathology; D005260:Female; D007113:Immunity, Innate / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D000067596:Interleukin-33; D015848:Interleukin-5 / Q000097:blood; D007378:Interleukins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D009504:Neutrophils / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology
D018925:Chemokines; D004268:DNA-Binding Proteins; C506536:IL33 protein, human; D000067596:Interleukin-33; D015848:Interleukin-5; D007378:Interleukins; C499308:Rag2 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma