{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:48:54Z","timestamp":1791517734003,"version":"4.3.4"},"reference-count":34,"publisher":"Rockefeller University Press","issue":"12","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,11,17]]},"abstract":"<jats:p>Intraepithelial lymphocytes (IELs) play an important role in maintaining the physiology of the small intestine. The majority of mouse IELs express CD8\u03b1\u03b1 and are either \u03b3\u03b4 or \u03b1\u03b2 T cells. Although the development and homing of CD8\u03b1\u03b1 IELs have been studied in some detail, the factors controlling their homeostasis and positioning are incompletely understood. Here we demonstrate that G protein\u2013coupled receptor 18 (GPR18) is abundantly expressed in CD8\u03b1\u03b1 IELs and that mice lacking this orphan receptor have reduced numbers of \u03b3\u03b4T IELs. Mixed bone marrow chimera experiments reveal a markedly reduced contribution of GPR18-deficient cells to the CD8\u03b1\u03b1 IEL compartment and a reduction in the CD8\u03b1\u03b2 T cell subset. These defects could be rescued by transduction with a GPR18-expressing retrovirus. The GPR18-deficient \u03b3\u03b4T IELs that remained in mixed chimeras had elevated Thy1, and there were less granzyme B+ and V\u03b37+ cells, indicating a greater reduction in effector-type cells. Flow cytometric analysis indicated GPR18 deficiency more strongly affected the CD8\u03b1\u03b1 cells in the intraepithelial compared with the adjacent lamina propria compartment. These findings establish a requirement for GPR18 in CD8\u03b1\u03b1 and CD8\u03b1\u03b2 IELs, and we suggest the receptor has a role in augmenting the accumulation of CD8 T cells in the intraepithelial versus lamina propria compartment.<\/jats:p>","DOI":"10.1084\/jem.20140646","type":"journal-article","created":{"date-parts":[[2014,10,28]],"date-time":"2014-10-28T02:31:46Z","timestamp":1414463506000},"page":"2351-2359","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":86,"title":["GPR18 is required for a normal CD8\u03b1\u03b1 intestinal intraepithelial lymphocyte compartment"],"prefix":"10.1084","volume":"211","author":[{"given":"Xiaoming","family":"Wang","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute 1 and 2"},{"name":"Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143 1 and 2"},{"name":"Howard Hughes Medical Institute 1 and 2"},{"name":"Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayakazu","family":"Sumida","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute 1 and 2"},{"name":"Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143 1 and 2"},{"name":"Howard Hughes Medical Institute 1 and 2"},{"name":"Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason G.","family":"Cyster","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute 1 and 2"},{"name":"Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143 1 and 2"},{"name":"Howard Hughes Medical Institute 1 and 2"},{"name":"Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2014,10,27]]},"reference":[{"key":"2023072602043805100_bib1","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1007\/s00281-012-0316-x","article-title":"Intraepithelial lymphocytes in celiac disease immunopathology","volume":"34","author":"Abadie","year":"2012","journal-title":"Semin. 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