NFATc1 deficiency in T cells protects mice from experimental autoimmune encephalomyelitis

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 RORγT (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‐γ 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‐γ, both being relevant for the EAE development.