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Gpr83 expression is not required for the maintenance of intestinal immune homeostasis and regulation of T-cell-dependent colitis

By Christy Toms, Heidi Jessup, Claire Thompson, Dilair Baban, Kay Davies and Fiona Powrie

Abstract

Regulatory T (TR) cells are integral to the maintenance of intestinal homeostasis, where an intricate balance between tolerance and immunity must be maintained. Recently, studies have focused on the identification of molecules involved in the function and/or development of TR cells. One such molecule, the G-protein coupled receptor Gpr83, has been identified through gene expression analysis as being overexpressed within thymic and peripheral naturally arising regulatory T (nTR) cell populations. The aim of this study was to further define the characteristics of Gpr83 expression and to investigate the role of Gpr83 in TR-cell development and function through the generation and analysis of Gpr83-deficient mice. Following activation, naïve CD4+ T cells induce Gpr83 expression in a transforming growth factor (TGF)-β dependent manner. Rather than being a general marker of activation, Gpr83 expression could only be detected in cells also expressing forkhead/winged helix transcription factor (Foxp3), further supporting the association of Gpr83 with the regulatory cell phenotype. Mice deficient in Gpr83 expression developed normally and did not display signs of inflammatory disease. Thymic nTR-cell development was unaffected by a lack of Gpr83 expression and peripheral nTR-cell homeostasis was normal when compared with that of wild-type mice. Gpr83 expression was dispensable for the regulatory activity of nTR cells as Gpr83-deficient nTR cells could suppress the development of disease in a T-cell transfer model of colitis. These results suggest a redundant role for Gpr83 in the function of TR cells in this model of disease. Further studies are required to determine the role of Gpr83 in TR-cell biology

Topics: Original Articles
Publisher: Blackwell Science Inc
OAI identifier: oai:pubmedcentral.nih.gov:2669134
Provided by: PubMed Central
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