T cell-intrinsic ASC critically promotes T(H)17-mediated experimental autoimmune encephalomyelitis.
Bradley N MartinChenhui WangCun-jin ZhangZizhen KangMuhammet Fatih GulenJarod A ZeppJunjie ZhaoGuanglin BianJeong-su DoBooki MinPaul G PavicicCaroline El-SanadiPaul L FoxAoi AkitsuYoichiro IwakuraAnasuya SarkarMark D WewersWilliam J KaiserEdward S MocarskiMarc E RothenbergAmy G HiseGeorge R DubyakRichard M RansohoffXiaoxia LiPublished in: Nature immunology (2016)
Interleukin 1β (IL-1β) is critical for the in vivo survival, expansion and effector function of IL-17-producing helper T (T(H)17) cells during autoimmune responses, including experimental autoimmune encephalomyelitis (EAE). However, the spatiotemporal role and cellular source of IL-1β during EAE pathogenesis are poorly defined. In the present study, we uncovered a T cell-intrinsic inflammasome that drives IL-1β production during T(H)17-mediated EAE pathogenesis. Activation of T cell antigen receptors induced expression of pro-IL-1β, whereas ATP stimulation triggered T cell production of IL-1β via ASC-NLRP3-dependent caspase-8 activation. IL-1R was detected on T(H)17 cells but not on type 1 helper T (T(H)1) cells, and ATP-treated T(H)17 cells showed enhanced survival compared with ATP-treated T(H)1 cells, suggesting autocrine action of T(H)17-derived IL-1β. Together these data reveal a critical role for IL-1β produced by a T(H)17 cell-intrinsic ASC-NLRP3-caspase-8 inflammasome during inflammation of the central nervous system.
Keyphrases
- induced apoptosis
- cell cycle arrest
- oxidative stress
- cell death
- regulatory t cells
- multiple sclerosis
- dendritic cells
- poor prognosis
- nlrp inflammasome
- dna methylation
- cell therapy
- machine learning
- cell proliferation
- single cell
- bone marrow
- diabetic rats
- mesenchymal stem cells
- electronic health record
- deep learning
- free survival
- newly diagnosed