Yu, Jhang-SianJhang-SianYuHamada, MichitoMichitoHamadaOhtsuka, ShigeoShigeoOhtsukaYoh, KeigyouKeigyouYohTakahashi, SatoruSatoruTakahashiSHI-CHUEN MIAW2019-08-062019-08-0620171664-3224https://www.scopus.com/inward/record.uri?eid=2-s2.0-85032171395&doi=10.3389%2ffimmu.2017.01399&partnerID=40&md5=b5f416c1e31a3aebda38780e1cffb259https://scholars.lib.ntu.edu.tw/handle/123456789/416286c-Maf belongs to the large Maf family of transcription factors and plays a key role in the regulation of cytokine production and differentiation of TH2, TH17, TFH, and Tr1 cells. Invariant natural killer T (iNKT) cells can rapidly produce large quantity of TH-related cytokines such as IFN-γ, IL-4, and IL-17A upon stimulation by glycolipid antigens, such as α-galactosylceramide (α-GalCer). However, the role of c-Maf in iNKT cells and iNKT cells-mediated diseases remains poorly understood. In this study, we demonstrate that α-GalCer-stimulated iNKT cells express c-Maf transcript and protein. By using c-Maf-deficient fetal liver cell-reconstituted mice, we further show that c-Maf-deficient iNKT cells produce less IL-17A than their wild-type counterparts after α-GalCer stimulation. While c-Maf deficiency does not affect the development and activation of iNKT cells, c-Maf is essential for the induction of IL-17-producing iNKT (iNKT17) cells by IL-6, TGF-β, and IL-1β, and the optimal expression of RORγt. Accordingly, c-Maf-deficient iNKT17 cells lose the ability to recruit neutrophils into the lungs. Taken together, c-Maf is a positive regulator for the expression of IL-17A and RORγt in iNKT17 cells. It is a potential therapeutic target in iNKT17 cell-mediated inflammatory disease.enIL-17; airway neutrophilia; c-Maf; cytokine regulation; invariant natural killer T cellsjournal article10.3389/fimmu.2017.01399291634802-s2.0-85032171395WOS:000413831700001https://api.elsevier.com/content/abstract/scopus_id/85032171395