In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-08-21)
Abstract:
The outcome of T cell activation is determined by mechanisms that balance Ca 2+ influx and clearance. Here we report that murine CD4 T cells lacking Neuroplastin ( Nptn −/− ), an immunoglobulin superfamily protein, display elevated cytosolic Ca 2+ and impaired post-stimulation Ca 2+ 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 Ca 2+ 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 Ca 2+ handling. Supporting this, Ca 2+ extrusion was impaired while Ca 2+ levels in internal stores were increased. T cells heterozygous for PMCA1 mimicked the phenotype of Nptn −/− T cells. Consistent with sustained Ca 2+ 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.
Type of Medium:
Online Resource
ISSN:
2045-2322
DOI:
10.1038/s41598-017-08519-4
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2017
detail.hit.zdb_id:
2615211-3
Permalink