NF-κB is crucial in proximal T-cell signaling for calcium influx and NFAT activation

Crystina C. Bronk, Sean Yoder, Emily L. Hopewell, Shengyu Yang, Esteban Celis, Xue Zhong Yu, Amer A. Beg

Research output: Contribution to journalArticle

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3741-3746
Number of pages6
JournalEuropean Journal of Immunology
Volume44
Issue number12
DOIs
StatePublished - Jan 1 2014

Keywords

  • Gene expression
  • NF-κB
  • Signal transduction
  • T-cell activation
  • Transcription factors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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