{"doi":"10.1002/eji.201444904","title":"NF‐κB is crucial in proximal T‐cell signaling for calcium influx and NFAT activation","abstract":"<jats:p>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<jats:sup>+</jats:sup> 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<jats:sup>−/−</jats:sup>cRel<jats:sup>−/−</jats:sup>CD8<jats:sup>+</jats:sup> T cells had significantly diminished NFAT and AP‐1 activation compared with WT or PKCθ<jats:sup>−/−</jats:sup> CD8<jats:sup>+</jats:sup> 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<jats:sup>−/−</jats:sup>cRel<jats:sup>−/−</jats:sup> 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.</jats:p>","journal":"European Journal of Immunology","year":2014,"id":630569,"datarank":0.3958585994422889,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.0,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":255362,"name":"Sean Yoder","orcid":"0000-0002-3120-3279","position":1,"is_corresponding":false},{"id":1633634,"name":"Emily L. 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Genome‐wide transcriptional profiling following Ag‐induced CD8<jats:sup>+</jats:sup> 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<jats:sup>−/−</jats:sup>cRel<jats:sup>−/−</jats:sup>CD8<jats:sup>+</jats:sup> T cells had significantly diminished NFAT and AP‐1 activation compared with WT or PKCθ<jats:sup>−/−</jats:sup> CD8<jats:sup>+</jats:sup> 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<jats:sup>−/−</jats:sup>cRel<jats:sup>−/−</jats:sup> 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. 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