Notch signaling regulates PD-1 expression during CD8+ T-cell activation View Full Text


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Article Info

DATE

2013-01

AUTHORS

Mélissa Mathieu, Natacha Cotta-Grand, Jean-François Daudelin, Paméla Thébault, Nathalie Labrecque

ABSTRACT

Programmed cell death 1 (PD-1) is an inhibitory receptor involved in T-cell activation, tolerance and exhaustion. Little is known on how the expression of PD-1 is controlled during T-cell activation. Recent studies demonstrated that NFATc1 and IRF9 regulate Pdcd1 (PD-1) transcription and that T-bet acts as a transcriptional repressor. In this study, we have investigated the role of the Notch signaling pathway in PD-1 regulation. Using specific inhibitors of the Notch signaling pathway, we showed decreased PD-1 expression and inhibition of Pdcd1 transcription by activated CD8(+) T cells. Chromatin immunoprecipitation further showed occupancy of the Pdcd1 promoter with RBPJk and Notch1 intracellular domain at RBPJk-binding sites. Our results identify the Notch signaling pathway as an important regulator of PD-1 expression by activated CD8(+) T cells. More... »

PAGES

82

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/icb.2012.53

DOI

http://dx.doi.org/10.1038/icb.2012.53

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1049831238

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23070399


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