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MRTF-SRF signalling in the T cell IL2 response

ABSTRACT: The transcription factor SRF is a master regulator of growth factor inducible and cytoskeletal gene expression. Two transcription cofactor families, the TCFs & the MRTFs, are responsible for SRF's activity to direct transcriptional programme in response to extracellular signalling through the Ras-ERK and Rho-actin pathways respectively. We are investigating the role of the SRF network in the response to infection, using the Listeria monocytogenes model. We find that inactivation of the network impairs the ability of CD8 T cells to proliferate in response to listeria and to generate memory cells. Surprisingly, the defect reflects impaired MRTF-SRF signalling rather than the TCF-SRF signalling pathway usually associated with proliferation. Moreover, the defec doesn'tt lie downstream of the initial activation of the TCR, appearing instead to arise from an inability of CD8 T cells to present IL-2 to each other in paracrine fashion. Consistent with these observations, we find that while cultured CD8 MRTF-null T cells can be effectively activated by TCR crosslinking invitro, their ability to form clusters, which is IL-2-dependent, is impaired. Moreover, as expected, pilot experiments indicate that these cells exhibit deficits both in the basal levels of MRTF-SRF target gene expression, and in their ability to induce these genes in response to IL-2 stimulation:

ORGANISM(S): Mus musculus

PROVIDER: GSE241689 | GEO | 2023/10/23

REPOSITORIES: GEO

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