| First Author | Zhi L | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 4 | Pages | 1639-47 |
| PubMed ID | 22798682 | Mgi Jnum | J:189744 |
| Mgi Id | MGI:5446950 | Doi | 10.4049/jimmunol.1200528 |
| Citation | Zhi L, et al. (2012) Enhanced Th17 differentiation and aggravated arthritis in IEX-1-deficient mice by mitochondrial reactive oxygen species-mediated signaling. J Immunol 189(4):1639-47 |
| abstractText | 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. |
