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

6 Citations (Scopus)

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

Fingerprint

Calcium Signaling
T-Lymphocytes
Transcription Factor AP-1
Inbred C57BL Mouse
Signal Transduction
Transcription Factors
Genome
Pharmacology
Calcium

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

NF-κB is crucial in proximal T-cell signaling for calcium influx and NFAT activation. / Bronk, Crystina C.; Yoder, Sean; Hopewell, Emily L.; Yang, Shengyu; Celis, Esteban; Yu, Xue Zhong; Beg, Amer A.

In: European Journal of Immunology, Vol. 44, No. 12, 01.01.2014, p. 3741-3746.

Research output: Contribution to journalArticle

Bronk, Crystina C. ; Yoder, Sean ; Hopewell, Emily L. ; Yang, Shengyu ; Celis, Esteban ; Yu, Xue Zhong ; Beg, Amer A. / NF-κB is crucial in proximal T-cell signaling for calcium influx and NFAT activation. In: European Journal of Immunology. 2014 ; Vol. 44, No. 12. pp. 3741-3746.
@article{d7f8396ac6b54501b42d6fe6e0470f2e,
title = "NF-κB is crucial in proximal T-cell signaling for calcium influx and NFAT activation",
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.",
keywords = "Gene expression, NF-κB, Signal transduction, T-cell activation, Transcription factors",
author = "Bronk, {Crystina C.} and Sean Yoder and Hopewell, {Emily L.} and Shengyu Yang and Esteban Celis and Yu, {Xue Zhong} and Beg, {Amer A.}",
year = "2014",
month = "1",
day = "1",
doi = "10.1002/eji.201444904",
language = "English (US)",
volume = "44",
pages = "3741--3746",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "12",

}

TY - JOUR

T1 - NF-κB is crucial in proximal T-cell signaling for calcium influx and NFAT activation

AU - Bronk, Crystina C.

AU - Yoder, Sean

AU - Hopewell, Emily L.

AU - Yang, Shengyu

AU - Celis, Esteban

AU - Yu, Xue Zhong

AU - Beg, Amer A.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

KW - Gene expression

KW - NF-κB

KW - Signal transduction

KW - T-cell activation

KW - Transcription factors

UR - http://www.scopus.com/inward/record.url?scp=84924322584&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84924322584&partnerID=8YFLogxK

U2 - 10.1002/eji.201444904

DO - 10.1002/eji.201444904

M3 - Article

C2 - 25251667

AN - SCOPUS:84924322584

VL - 44

SP - 3741

EP - 3746

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 12

ER -