NFATc1 deficiency in T cells protects mice from experimental autoimmune encephalomyelitis
| العنوان: | NFATc1 deficiency in T cells protects mice from experimental autoimmune encephalomyelitis |
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| المؤلفون: | Susetta Finotto, Lena Sandrock, Corinna Holzinger, Elisabeth Zinser, Sonja Koch, Sarah Reppert |
| المصدر: | European Journal of Immunology |
| بيانات النشر: | Wiley, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | NFAT, Encephalomyelitis, Autoimmune, Experimental, T-Lymphocytes, Immunology, Down-Regulation, Biology, Immunomodulation, Transforming Growth Factor beta1, Interferon-gamma, Mice, CD4+ T cells, RAR-related orphan receptor gamma, medicine, Animals, Immunology and Allergy, RORγT, RNA, Messenger, Transcription factor, Mice, Knockout, Orphan receptor, NFATC Transcription Factors, integumentary system, EAE, Interleukins, Interleukin-17, Experimental autoimmune encephalomyelitis, Regular Article, Cell Differentiation, Receptors, Interleukin, Nuclear Receptor Subfamily 1, Group F, Member 3, Th1 Cells, medicine.disease, Interleukin-10, Cell biology, Mice, Inbred C57BL, Calcineurin, Cancer research, Cytokines, Th17 Cells, Th17, Spleen, CD8 |
| الوصف: | 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. |
| تدمد: | 1521-4141 0014-2980 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2402fa26c1edf03a0ce2ea85a500978fTest https://doi.org/10.1002/eji.201445150Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2402fa26c1edf03a0ce2ea85a500978f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15214141 00142980 |
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