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

作者：Bronk Crystina C; Yoder Sean; Hopewell Emily L; Yang Shengyu; Celis Esteban; Yu Xue Zhong; Beg Amer A^*

来源：European Journal of Immunology, 2014, 44(12): 3741-3746.

DOI：10.1002/eji.201444904

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

In the accepted model of T-cell activation, parallel signal-transduction pathways activate the transcription factors NF-kappa B, 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-kappa B p50 and cRel subunits. Importantly, p50(-/-)cRel(-/-)CD8(+) T cells had significantly diminished NFAT and AP-1 activation compared with WT or PKC theta(-/-) CD8(+) T cells. Attenuated NFAT activation after TCR engagement was associated with reduced calcium influx, PLC gamma and Zap70 activation. Interestingly, pharmacological bypass of PLC.-regulated pathways largely rescued p50(-/-)cRel(-/-) T-cell proliferative defects. These results indicate a crucial and unexpected requirement for NF-kappa B 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-kappa B pathway components may be due to impaired proximal T-cell signaling.

• 出版日期2014-12