Normal Thymocyte Egress, T Cell Trafficking, and CD4+ T Cell Homeostasis Require Interactions between RGS Proteins and Gαi2.

Il-Young Hwang, Chung Park, Kathleen Harrison, John H Kehrl

Journal of immunology (Baltimore, Md. : 1950) 2017 Apr 01

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Adaptive immunity depends on mature thymocytes leaving the thymus to enter the bloodstream and the trafficking of T cells through lymphoid organs. Both of these require heterotrimeric Gαi protein signaling, whose intensity and duration are controlled by the regulator of G protein signaling (RGS) proteins. In this study, we show that RGS protein/Gαi2 interactions are essential for normal thymocyte egress, T cell trafficking, and homeostasis. Mature thymocytes with a Gαi2 mutation that disables RGS protein binding accumulated in the perivascular channels of thymic corticomedullary venules. Severe reductions in peripheral naive CD4+ T cells and regulatory T cells occurred. The mutant CD4+ T cells adhered poorly to high endothelial venules and exhibited defects in lymph node entrance and egress. The kinetics of chemokine receptor signaling were disturbed, including chemokine- induced integrin activation. Despite the thymic and lymph node egress defects, sphingosine-1-phosphate signaling was not obviously perturbed. This study reveals how RGS proteins modulate Gαi2 signaling to facilitate thymocyte egress and T cell trafficking.

Citation

Il-Young Hwang, Chung Park, Kathleen Harrison, John H Kehrl. Normal Thymocyte Egress, T Cell Trafficking, and CD4+ T Cell Homeostasis Require Interactions between RGS Proteins and Gαi2. Journal of immunology (Baltimore, Md. : 1950). 2017 Apr 01;198(7):2721-2734