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Giuseppina Marchesini Tovar, Tessa Bergsbaken, The role of GPR132 in regulating T cell function, The Journal of Immunology, Volume 210, Issue Supplement_1, May 2023, Page 239.13, https://doi.org/10.4049/jimmunol.210.Supp.239.13
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Abstract
CD8+ T cells are vital in controlling pathogens and undergo robust expansion upon priming. Tissue-resident memory T cells (Trm) that reside in non-lymphoid tissues are less responsive in terms of expansion; however, the signals within the tissue that direct the quantity and quality of CD8+ Trm pools are still unclear. G protein coupled receptors (GPCRs) sense and integrate environmental signals and are essential for regulating T cell function. GPR132 or G2A modulates homeostasis in mature peripheral T cells, and Gpr132−/− mice develop an autoimmune syndrome accompanied by expansion of the T cell compartment. GPR132 ligands are synthesized by intestinal epithelial cells and commensal bacteria, making GPR132 a potential target for regulating T cell expansion in the intestinal tissue. We investigated the function of GPR132 during intestinal infection by Y. pseudotuberculosis.GPR132 expression was elevated on T cells early after infection . Gpr132−/− cells displayed enhanced expansion, outnumbering wild-type (WT) cells by 3–4 fold in all tissues. Early differentiation was not impacted by GPR132-deficiency, as there were no differences in circulating and Trm memory precursor subpopulations between WT and Gpr132−/− cells. To dissect the mechanism of GPR132 action, we examined the transcriptome of WT and Gpr132−/− naïve T cells. Minimal differences in gene expression were observed, and both showed comparable proliferation upon TCR-engagement in vitro. These data suggest enhanced responsiveness of Gpr132−/−T cells was not programmed at the naïve stage but develops during T cell activation. Our results expose a role for GPR132 signaling axis in regulating T cell immunity and demonstrate GPCRs can be targeted to modulate T cell responses.
New Jersey Commission on Cancer Research Predoctoral Fellowship Grant COCR23PRF011.
