Article ; Online: STAT1 signaling protects self-reactive T cells from control by innate cells during neuroinflammation.
JCI insight
2022 Volume 7, Issue 12
Abstract: The transcription factor STAT1 plays a critical role in modulating the differentiation of CD4+ T cells producing IL-17 and GM-CSF, which promote the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS) ...
| Abstract | The transcription factor STAT1 plays a critical role in modulating the differentiation of CD4+ T cells producing IL-17 and GM-CSF, which promote the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). The protective role of STAT1 in MS and EAE has been largely attributed to its ability to limit pathogenic Th cells and promote Tregs. Using mice with selective deletion of STAT1 in T cells (STAT1CD4-Cre), we identified a potentially novel mechanism by which STAT1 regulates neuroinflammation independently of Foxp3+ Tregs. STAT1-deficient effector T cells became the target of NK cell-mediated killing, limiting their capacity to induce EAE. STAT1-deficient T cells promoted their own killing by producing more IL-2 that, in return, activated NK cells. Elimination of NK cells restored EAE susceptibility in STAT1CD4-Cre mice. Therefore, our study suggests that the STAT1 pathway can be manipulated to limit autoreactive T cells during autoimmunity directed against the CNS. |
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| MeSH term(s) | Animals ; Autoimmunity ; CD4-Positive T-Lymphocytes ; Encephalomyelitis, Autoimmune, Experimental ; Mice ; Multiple Sclerosis ; Neuroinflammatory Diseases ; STAT1 Transcription Factor/genetics ; STAT1 Transcription Factor/metabolism |
| Chemical Substances | STAT1 Transcription Factor ; Stat1 protein, mouse |
| Language | English |
| Publishing date | 2022-06-22 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural |
| ISSN | 2379-3708 |
| ISSN (online) | 2379-3708 |
| DOI | 10.1172/jci.insight.148222 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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