Cish inhibits CD8+ T cell immunity and disrupts proximal T cell receptor signaling

ABSTRACT: T cell receptor (TCR) signaling is a critical process in immunity to infectious disease and cancer. Recently, a genome-wide association study has implicated polymorphisms in the CISH locus with susceptibility to infectious diseases. However, the role of Cish in the immune responses and its molecular underpinnings remains unclear. Here we demonstrate that Cish deletion resulted in protection against viral infection and enhanced CD8+ T cell tumor immunity. Transcriptome profiling revealed a hyper-TCR activation signature in Cish-deficient CD8+ T cells. Subsequent analysis revealed an inhibitory role for Cish in PLCγ1 activation, ensuing Ca2+ release and downstream signaling. In the steady-state Cish was found to physically interact with PLCγ1, however, PLCγ1 was only found to be ubiquitinate

ORGANISM(S): Mus musculus

SUBMITTER: Shashank Patel 

PROVIDER: E-GEOD-56328 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress