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Mutations in human\n                    <jats:italic>IRGM<\/jats:italic>\n                    and genetic deletion of mouse\n                    <jats:italic>Irgm1<\/jats:italic>\n                    have been linked to increased severity of inflammatory bowel disease, cancer, sepsis, and various infections. While IRGM\/Irgm1 are known cell\u2010intrinsic regulators of inflammation, their roles in T cell function remain poorly understood. We previously demonstrated that Irgm1 deficiency leads to increased production of proinflammatory mediators, including Granzyme B and interferon\u2010\u03b3, and increased apoptosis in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Here, we show that Irgm1 deficiency also alters Granzyme B production and impairs virus\u2010specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses during lymphocytic choriomeningitis virus (LCMV) infection. Using T cell\u2010specific Irgm1 knockout mice and adoptive transfer experiments, we unexpectedly found that Irgm1 regulates CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses through a cell\u2010extrinsic mechanism. Transcriptomic and genetic analyses identified type I interferons (IFNs) as key mediators of this effect. These findings reveal a previously unrecognized, cell\u2010extrinsic role for Irgm1 in regulating CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell survival and function by modulating the inflammatory environment. Our results suggest that IRGM\/Irgm1 acts as a critical immune rheostat, restraining pathological inflammation and modulating T cell responses in infection and autoimmunity.\n                  <\/jats:p>","DOI":"10.1002\/eji.70113","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T06:39:52Z","timestamp":1774852792000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Irgm1 Restrains CD8\n                    <sup>+<\/sup>\n                    T Cell Cytokine Production and Apoptosis via Cell\u2010Extrinsic Regulation of Type I Interferon Signaling"],"prefix":"10.1002","volume":"56","author":[{"given":"Caitlyn T.","family":"Molloy","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yazan","family":"Alwarawrah","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Pediatric Endocrinology University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan A.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Genetics University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian E.","family":"Fee","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Geriatrics and Center for the Study of Aging and Human Development Duke University Medical Center  Durham North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason K.","family":"Whitmire","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of North Carolina  Chapel Hill North Carolina USA"},{"name":"Department of Genetics University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory A.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Geriatrics and Center for the Study of Aging and Human Development Duke University Medical Center  Durham North Carolina USA"},{"name":"Department of Molecular Genetics and Microbiology Duke University Medical Center  Durham North Carolina USA"},{"name":"Department of Integrative Immunobiology Duke University Medical Center  Durham North Carolina USA"},{"name":"Geriatric Research, Education, and Clinical Center Durham VA Health Care System  Durham North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3676-9391","authenticated-orcid":false,"given":"Nancie 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