1. NF-κB is crucial in proximal T-cell signaling for calcium influx and NFAT activation.
- Author
-
Bronk CC, Yoder S, Hopewell EL, Yang S, Celis E, Yu XZ, and Beg AA
- Subjects
- Animals, CD8-Positive T-Lymphocytes cytology, Calcium Signaling genetics, Cell Proliferation physiology, Mice, Mice, Knockout, NF-kappa B p50 Subunit genetics, NFATC Transcription Factors genetics, Phospholipase C gamma genetics, Phospholipase C gamma immunology, Proto-Oncogene Proteins c-rel genetics, Receptors, Antigen, T-Cell genetics, Receptors, Antigen, T-Cell immunology, ZAP-70 Protein-Tyrosine Kinase genetics, ZAP-70 Protein-Tyrosine Kinase immunology, CD8-Positive T-Lymphocytes immunology, Calcium Signaling immunology, NF-kappa B p50 Subunit immunology, NFATC Transcription Factors immunology, Proto-Oncogene Proteins c-rel immunology
- Abstract
In the accepted model of T-cell activation, parallel signal-transduction pathways activate the transcription factors NF-κB, NFAT, and AP-1 to drive clonal expansion of T cells in response to Ag. Genome-wide transcriptional profiling following Ag-induced CD8(+) T-cell activation in C57BL/6 mouse T cells revealed that genes regulated by NFAT were also reduced in the absence of NF-κB p50 and cRel subunits. Importantly, p50(-/-) cRel(-/-) CD8(+) T cells had significantly diminished NFAT and AP-1 activation compared with WT or PKCθ(-/-) CD8(+) T cells. Attenuated NFAT activation after TCR engagement was associated with reduced calcium influx, PLCγ and Zap70 activation. Interestingly, pharmacological bypass of PLCγ-regulated pathways largely rescued p50(-/-) cRel(-/-) T-cell proliferative defects. These results indicate a crucial and unexpected requirement for NF-κB p50 and cRel subunits in proximal TCR signaling and calcium responses. They further suggest that key defects in T cells in the absence of NF-κB pathway components may be due to impaired proximal T-cell signaling., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2014
- Full Text
- View/download PDF