Snai2 and Snai3 transcriptionally regulate cellular fitness and functionality of T cell lineages through distinct gene programs

T lymphocytes are essential contributors to the adaptive immune system and consist of multiple lineages that serve various effector and regulatory roles. As such, precise control of gene expression is essential to the proper development and function of these cells. Previously, we identified Snai2 and Snai3 as being essential regulators of immune tolerance partly due to the impaired function of CD4+ regulatory T cells in Snai2/3 conditional double knockout mice. Here we extend those previous findings using a bone marrow transplantation model to provide an environmentally unbiased view of the molecular changes imparted onto various T lymphocyte populations once Snai2 and Snai3 are deleted. The data presented here demonstrate that Snai2 and Snai3 transcriptionally regulate the cellular fitness and functionality of not only CD4+ regulatory T cells but effector CD8a+ and CD4+ conventional T cells as well. This is achieved through the modulation of gene sets unique to each cell type and includes transcriptional targets relevant to the survival and function of each T cell lineage. As such, Snai2 and Snai3 are essential regulators of T cell immunobiology. Overall design: GFP- CD3e+ CD8a+ CD4-, GFP- CD3e+ CD8a- CD4+ CD25- and GFP- CD3e+ CD8a- CD4+ CD25+ T cells were isolated from spleens of UBC-GFP mice transplanted with WT or cDKO lineage-depleted donor bone marrow following lethal irradiation of recipient mice. RNA-seq was performed on 3-4 biological replicates from each genotype for all T cell populations analyzed.

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Pioli PD, Whiteside SK, Weis JJ, Weis JH