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Series GSE56328 Query DataSets for GSE56328
Status Public on Apr 30, 2015
Title Cish inhibits CD8+ T cell immunity and disrupts proximal T cell receptor signaling
Organism Mus musculus
Experiment type Expression profiling by array
Summary 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 ubiquitinated after acute TCR stimulation in the presence of Cish. These data implicate Cish as a potent negative regulator of TCR signaling and T cell immunity to infection and cancer and may have significant clinical applications.
Overall design 4 biological replicates from wild-type mice and 3 biological replicates from Cish knock-out (-/-) mice were analyzed.
Contributor(s) Palmer D, Restifo N
Citation(s) 26527801
Submission date Mar 28, 2014
Last update date Mar 04, 2019
Contact name Shashank Patel
Organization name NCI, NIH
Street address 10 Center Drive; Bldg10-CRC, Room 3-5816W
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (1)
GPL6246 [MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version]
Samples (13)
GSM1359200 WT CD8 T cell-stim 2 hr-01
GSM1359201 WT CD8 T cell-stim 2 hr-02
GSM1359202 WT CD8 T cell-stim 2 hr-03
BioProject PRJNA242918

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Supplementary file Size Download File type/resource
GSE56328_RAW.tar 56.2 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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