| First Author | Reppert S | Year | 2015 |
| Journal | Eur J Immunol | Volume | 45 |
| Issue | 5 | Pages | 1426-40 |
| PubMed ID | 25689841 | Mgi Jnum | J:229727 |
| Mgi Id | MGI:5753043 | Doi | 10.1002/eji.201445150 |
| Citation | Reppert S, et al. (2015) NFATc1 deficiency in T cells protects mice from experimental autoimmune encephalomyelitis. Eur J Immunol 45(5):1426-40 |
| abstractText | NFATc1 is a member of the nuclear factor of activated T cells (NFAT) family of transcription factors. NFAT is activated upon T-cell receptor activation followed by intracytoplasmatic calcium influx where calmodulin, a calcium sensor protein, activates the phosphatase calcineurin that dephosphorylates NFAT proteins and results in NFAT nuclear import. Here, we show the analysis of conditional NFATc1-deficient mice bearing a deletion of NFATc1 in CD4(+) and CD8(+) T cells. NFATc1-deficient CD4(+) T cells polarized under Th17 conditions express reduced levels of the Th17-associated transcription factor RORgammaT (where ROR is RAR-related orphan receptor) as well as the Th17-associated cytokines IL-17A, IL-17F, IL-21, and IL-10. In the murine model of experimental EAE, we found a strong reduction of the disease outcome in conditional NFATc1-deficient mice, as compared with control littermates. This was accompanied by a diminished inflammation in the brain and spinal cord and reduced IL-17A and IFN-gamma expression by antigen-specific spleen, spinal cord, and brain cells. Altogether, these results reveal an important role of NFATc1 in inducing Th17-cell responses and IFN-gamma, both being relevant for the EAE development. |
