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RESEARCH PRODUCT
Fas signaling-mediated T
Shen YingyingSong ZhengboLu XinliangMa ZeyuLu ChaojieZhang BeiChen YinghuDuan MengApetoh LionelLi XuGuo JufengMiao YingZhang GenshengYang DiyaCai ZhijianWang Jianlisubject
Mice Inbred BALB CNFATC Transcription FactorsNF-kappa BMice NudeCell DifferentiationCancer immunotherapySignal transductionInflammatory Bowel DiseasesT-Lymphocytes Regulatoryp38 Mitogen-Activated Protein KinasesArticleMice Inbred C57BLMiceLymphocyte differentiationNeoplasmsProtein Kinase C betaAnimalsCytokinesHumansFemalefas ReceptorCD4-positive T cellsdescription
Fas induces apoptosis in activated T cell to maintain immune homeostasis, but the effects of non-apoptotic Fas signaling on T cells remain unclear. Here we show that Fas promotes TH9 cell differentiation by activating NF-κB via Ca2+-dependent PKC-β activation. In addition, PKC-β also phosphorylates p38 to inactivate NFAT1 and reduce NFAT1-NF-κB synergy to promote the Fas-induced TH9 transcription program. Fas ligation exacerbates inflammatory bowel disease by increasing TH9 cell differentiation, and promotes antitumor activity in p38 inhibitor-treated TH9 cells. Furthermore, low-dose p38 inhibitor suppresses tumor growth without inducing systemic adverse effects. In patients with tumor, relatively high TH9 cell numbers are associated with good prognosis. Our study thus implicates Fas in CD4+ T cells as a target for inflammatory bowel disease therapy. Furthermore, simultaneous Fas ligation and low-dose p38 inhibition may be an effective approach for TH9 cell induction and cancer therapy.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2018-10-26 | Nature communications |