title: Normal Thymocyte Egress, T Cell Trafficking, and CD4+T Cell Homeostasis Require Interactions between RGS Proteins and Gαi2.
abstract: 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 Gαiprotein signaling, whose intensity and duration are controlled by the regulator of G protein signaling (RGS) proteins. In this study, we show that RGS protein/Gαi2interactions are essential for normal thymocyte egress, T cell trafficking, and homeostasis. Mature thymocytes with a Gαi2mutation 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 Gαi2signaling to facilitate thymocyte egress and T cell trafficking.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Il-Young
authors.initials: IY
authors.lastname: Hwang
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Chung
authors.initials: C
authors.lastname: Park
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Harrison
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 jkehrl@niaid.nih.gov.
authors.forename: John H
authors.identifier: 0000-0002-6526-159X
authors.initials: JH
authors.lastname: Kehrl
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D005434:Flow Cytometry; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D020710:RGS Proteins / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D060168:Thymocytes / Q000276:immunology*
chemical_list: D020710:RGS Proteins; C107413:RGS16 protein; D051960:GTP-Binding Protein alpha Subunit, Gi2; C498016:Gnai2 protein, mouse