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RNA-seq of wild type and Slc25a3-deficient CD8 T cells

ABSTRACT: RNA-sequencing and analysis of in vitro differentiated CD8 T cells isolated from WT and Slc25a3-fl/fl Cd4-cre mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE212298 | GEO | 2023/09/22

REPOSITORIES: GEO

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Project description:Transforming growth factor-Î² (TGF-Î²) has been implicated in the control of differentiation and proliferation of multiple cell types. However, a role for TGF-Î² in the control of immune homeostasis is not fully understood because of its pleiotropic action. Here we report that complete ablation of the TGF-Î² signaling in T cells engendered aggressive early-onset, multiorgan, autoimmune-associated lesions with 100% mortality. Peripheral CD4+ and CD8+ T cells with TGF-Î²-receptor II (TGF-Î²RII) deficiency activated cytolytic and T helper 1 (Th1) differentiation program in a cell-intrinsic T cell receptor (TCR)-specific fashion. Furthermore, TGF-Î²RII deficiency blocked the development of canonical CD1d-restricted NKT cells. Instead, it facilitated generation of a highly pathogenic T cell subset exhibiting multiple hallmarks of NK cells and sharply elevated amounts of FasL, perforin, granzymes, and interferon-Î³. Thus, TGF-Î² signaling in peripheral T cells is crucial in restraining TCR activation-dependent Th1, cytotoxic, and NK cell-like differentiation program which, when left unchecked, leads to rapidly progressing fatal autoimmunity. Experiment Overall Design: To better understand the basis for pathogenicity of TGF-Î²RII-deficient NK1.1+ T cells, we performed gene expression profiling of NK1.1+ and NK1.1â T cell subsets from Tgfbr2fl/fl x CD4-Cre mice. We limited our analysis to CD8+ T cell subsets because NK1.1+ CD8 T cells made up 70% of total NK1.1+ T cells in Tgfbr2fl/fl x CD4-Cre mice, and this T cell subset showed the greatest numerical increase compared to littermate control mice. Thus, in these experiments we used FACS-sorted NK1.1+ and NK1.1â CD8+ T cells from 15- to 17-day-old mutant mice and total CD8+ T cells from Tgfbr2fl/wt x CD4-Cre littermate controls. Experiment Overall Design: mRNA expression profiles of NK1.1+ and NK1.1â CD8+ T cells from Tgfbr2fl/fl x CD4-Cre (KO) mice were compared to NK1.1â T cells from littermate control Tgfbr2fl/WT x CD4-Cre (Control) mice.

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RNA-seq of wild type and Slc25a3-deficient CD8 T cells

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