Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells.

ABSTRACT: While inhibition of T cell co-inhibitory receptors has revolutionized cancer therapy, the mechanisms governing their expression on human T cells have not been elucidated. Type 1 interferon (IFN-I) modulates T cell immunity in viral infection, autoimmunity, and cancer, and may facilitate induction of T cell exhaustion in chronic viral infection. Here we show that IFN-I regulates co-inhibitory receptor expression on human T cells, inducing PD-1/TIM-3/LAG-3 while surprisingly inhibiting TIGIT expression. High-temporal-resolution mRNA profiling of IFN-I responses enabled the construction of dynamic transcriptional regulatory networks uncovering three temporal transcriptional waves. Perturbation of key transcription factors on human primary T cells revealed unique regulators that control expres

SUBMITTER: Hafler D 

PROVIDER: S-EPMC8202434 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature