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The human <jats:italic>IRGM<\/jats:italic> gene has been strongly associated with Crohn\u2019s disease and other inflammatory diseases through  Genome-Wide Association\u00a0studies. Absence of <jats:italic>Irgm1<\/jats:italic> in mice prompts intestinal inflammation, autoimmunity, and impaired immune control of pathogenic bacteria and protozoa. Although prior work has focused on a prominent role for IRGM\/Irgm1 in regulating macrophage function, the work described here addresses a potential role of Irgm1 in regulating the function of mature T cells. Irgm1 was found to be highly expressed in T cells in a manner that varied with the particular T cell subset and increased with activation. Mice with a complete lack of Irgm1, or a conditional lack of Irgm1 specifically in T cells, displayed numerous changes in T cell numbers and function in all subsets examined, including CD4<jats:sup>+<\/jats:sup> (Th1 and Treg) and CD8<jats:sup>+<\/jats:sup> T cells. Related to changes in T cell number, apoptosis was found to be increased in Irgm1-deficient CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells. Altered T cell metabolism appeared to be a key driver of the phenotypes: Glucose metabolism and glycolysis were increased in Irgm1-deficient CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells, and muting these effects with glycolytic inhibitors partially restored T cell function and viability.<\/jats:p>","DOI":"10.1038\/s41598-021-04442-x","type":"journal-article","created":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T11:03:22Z","timestamp":1642417402000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Irgm1 regulates metabolism and function in T cell subsets"],"prefix":"10.1038","volume":"12","author":[{"given":"Yazan","family":"Alwarawrah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Danzaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda G.","family":"Nichols","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian E.","family":"Fee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Bock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Kucera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura P.","family":"Hale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory A.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancie J.","family":"MacIver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,17]]},"reference":[{"key":"4442_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2016.04.032","author":"D Pilla-Moffett","year":"2016","unstructured":"Pilla-Moffett, D., Barber, M. 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