期刊
SCIENTIFIC REPORTS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-017-08519-4
关键词
-
资金
- Deutsche Forschungsgemeinschaft [SFB854-B08, SFB854-A04, SFB854-Z]
- BMBF [CHL15WTZ-IB-049]
- ABINEP graduate school - Ministry for Economics, Science, and Digitization of the State Saxony-Anhalt
- European Fonds for Social and Regional Development (EFRE, ESF)
- [DFG-SFB426]
The outcome of T cell activation is determined by mechanisms that balance Ca2+ influx and clearance. Here we report that murine CD4 T cells lacking Neuroplastin (Nptn(-/-)), an immunoglobulin superfamily protein, display elevated cytosolic Ca2+ and impaired post-stimulation Ca2+ clearance, along with increased nuclear levels of NFAT transcription factor and enhanced T cell receptor-induced cytokine production. On the molecular level, we identified plasma membrane Ca2+ ATPases (PMCAs) as the main interaction partners of Neuroplastin. PMCA levels were reduced by over 70% in Nptn(-/-) T cells, suggesting an explanation for altered Ca2+ handling. Supporting this, Ca2+ extrusion was impaired while Ca2+ levels in internal stores were increased. T cells heterozygous for PMCA1 mimicked the phenotype of Nptn(-/-) T cells. Consistent with sustained Ca2+ levels, differentiation of Nptn(-/-) T helper cells was biased towards the Th1 versus Th2 subset. Our study thus establishes Neuroplastin-PMCA modules as important regulators of T cell activation.
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