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STIM1 controls T cell mediated immune regulation and inflammation in chronic infection

ABSTRACT: Influence of STIM1 on the transcriptome of CD4+ T cell subsets STIM1 is critical for the regulation of the intracellular Ca2+ homeostasis in CD4+ T cell. Loss of function mutations in STIM1 in patients result in severe immuno deficiency and recurrent infections. Using conditional knock out mice for STIM1, we investigated the role of STIM1 in T cells during chronic infections by in-vivo and in-vitro experiments. We found that STIM1 is required for T cell-mediated immunity to chronic infection with Mycobacterium tuberculosis (Mtb) as STIM1-deficient mice succumb to infection faster than littermate controls, have increased mycobacterial burdens and severe pulmonary infiltration with myeloid and lymphoid cells .Using the Affymetrix Mouse Exon 1.0 platform, we analyzed the influence of STIM1 expression on the transcriptom of CD4+T cells in-vitro. We found that STIM1 is required for the regulation of apoptosis related genes after TCR stimulation as well as for the induction of a transcriptonal program that polarizes naive CD4+ T cells into inducible CD4+ T regulatory cells (iTreg). Together with our in-vivo findings, these experiments reveal that STIM1 is essential for immune regulation to prevent an injurious inflammatory response during chronic infection.

ORGANISM(S): Mus musculus

PROVIDER: GSE66933 | GEO | 2015/03/17

SECONDARY ACCESSION(S): PRJNA278467

REPOSITORIES: GEO

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