NFATc1 deficiency in T cells protects mice from experimental autoimmune encephalomyelitis

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Abstract

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.

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APA

Reppert, S., Zinser, E., Holzinger, C., Sandrock, L., Koch, S., & Finotto, S. (2015). NFATc1 deficiency in T cells protects mice from experimental autoimmune encephalomyelitis. European Journal of Immunology, 45(5), 1426–1440. https://doi.org/10.1002/eji.201445150

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