title: GPR18 Controls Reconstitution of Mouse Small Intestine Intraepithelial Lymphocytes following Bone Marrow Transplantation.
abstract: Specific G protein coupled receptors (GPRs) regulate the proper positioning, function, and development of immune lineage subsets. Here, we demonstrate that GPR18 regulates the reconstitution of intraepithelial lymphocytes (IELs) of the small intestine following bone marrow transplantation. Through analysis of transcriptional microarray data, we find that GPR18 is highly expressed in IELs, lymphoid progenitors, and mature follicular B cells. To establish the physiological role of this largely uncharacterized GPR, we generated Gpr18-/- mice. Despite high levels of GPR18 expression in specific hematopoietic progenitors, Gpr18-/- mice have no defects in lymphopoiesis or myelopoiesis. Moreover, antibody responses following immunization with hapten-protein conjugates or infection with West Nile virus are normal in Gpr18-/- mice. Steady-state numbers of IELs are also normal in Gpr18-/- mice. However, competitive bone marrow reconstitution experiments demonstrate that GPR18 is cell-intrinsically required for the optimal restoration of small intestine TCRγδ+ and TCRαβ+ CD8αα+ IELs. In contrast, GPR18 is dispensable for the reconstitution of large intestine IELs. Moreover, Gpr18-/- bone marrow reconstitutes small intestine IELs similarly to controls in athymic recipients. Gpr18-/- chimeras show no changes in susceptibility to intestinal insults such as Citrobacter rodentium infections or graft versus host disease. These data reveal highly specific requirements for GPR18 in the development and reconstitution of thymus-derived intestinal IEL subsets in the steady-state and after bone marrow transplantation.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Becker
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Derrick J
authors.initials: DJ
authors.lastname: Callahan
authors.affiliation: Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, United States of America; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Richner
authors.affiliation: Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, United States of America; Division of Oncology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Jaebok
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, United States of America; Division of Oncology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: John F
authors.initials: JF
authors.lastname: DiPersio
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, United States of America; Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, United States of America; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Deepta
authors.initials: D
authors.lastname: Bhattacharya
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D002954:Citrobacter; D005260:Female; D006086:Graft vs Host Disease; D006412:Hematopoietic Stem Cells / Q000166:cytology; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D038042:Myelopoiesis; D020411:Oligonucleotide Array Sequence Analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism; D014184:Transplantation, Homologous; D014902:West Nile virus
chemical_list: C571204:GPR18 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D043562:Receptors, G-Protein-Coupled