NF-κB is crucial in proximal T-cell signaling for calcium influx and NFAT activation.
Eur J Immunol
; 44(12): 3741-6, 2014 Dec.
Article
en En
| MEDLINE
| ID: mdl-25251667
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos T CD8-positivos
/
Señalización del Calcio
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Proteínas Proto-Oncogénicas c-rel
/
Subunidad p50 de NF-kappa B
/
Factores de Transcripción NFATC
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos