期刊
JOURNAL OF IMMUNOLOGY
卷 189, 期 4, 页码 1639-1647出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1200528
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资金
- National Institutes of Health [AI050822, AI070785]
- Senior Research Award from the Crohn's and Colitis Foundation of America
CD4(+) Th1 and Th17 cells both can cause autoimmune diseases, either alone or collaboratively, if left unchecked. However, what determines the dominant Th effector phenotype in a specific autoimmune disease remains poorly understood. Our present investigation shows that null mutation of IEX-1 promotes differentiation of Th17 cells but compromises the survival of Th1 cells. The differential effect gave rise to a greater number of Th17 cells, a higher level of IL-17 production, and more severe arthritis in IEX-1 knockout mice than in wild-type mice after immunizations with collagen. IEX-1 deficiency-facilitated Th17 cell differentiation was mediated by the increased formation of reactive oxygen species (ROS) at mitochondria following T cell activation, as suggested by marked inhibition of Th17 induction with ROS scavenger N-acetylcysteine or mitoquinone, a specific inhibitor for mitochondrial ROS production. Mitochondrial ROS augmented the expression of B cell-activating transcription factor, which may contribute to increased IL-17 production in the absence of IEX-1, in light of its importance in IL-17 transcription. The results demonstrate that mitochondrial ROS contribute significantly to the dominant Th effector phenotype in autoimmunity in addition to the cytokine milieu. The Journal of Immunology, 2012, 189: 1639-1647.
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