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Irgm1 regulates metabolism and function in T cell subsets.
Alwarawrah, Yazan; Danzaki, Keiko; Nichols, Amanda G; Fee, Brian E; Bock, Cheryl; Kucera, Gary; Hale, Laura P; Taylor, Gregory A; MacIver, Nancie J.
Afiliación
  • Alwarawrah Y; Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes, University of North Carolina, Chapel Hill, NC, USA.
  • Danzaki K; Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes, Duke University Medical Center, Durham, NC, USA.
  • Nichols AG; Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes, University of North Carolina, Chapel Hill, NC, USA.
  • Fee BE; Department of Medicine, Division of Geriatrics, and Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, NC, USA.
  • Bock C; Geriatric Research, Education, and Clinical Center, Durham VA Health Care System, Durham, NC, USA.
  • Kucera G; Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
  • Hale LP; Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
  • Taylor GA; Department of Pathology, Duke University Medical Center, Durham, NC, USA.
  • MacIver NJ; Department of Medicine, Division of Geriatrics, and Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, NC, USA. gregory.taylor@duke.edu.
Sci Rep ; 12(1): 850, 2022 01 17.
Article en En | MEDLINE | ID: mdl-35039539
Immunity Related GTPases (IRG) are a family of proteins produced during infection that regulate membrane remodeling events in cells, particularly autophagy and mitophagy. The human IRGM gene has been strongly associated with Crohn's disease and other inflammatory diseases through Genome-Wide Association studies. Absence of Irgm1 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+ (Th1 and Treg) and CD8+ T cells. Related to changes in T cell number, apoptosis was found to be increased in Irgm1-deficient CD4+ and CD8+ 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+ and CD8+ T cells, and muting these effects with glycolytic inhibitors partially restored T cell function and viability.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Subgrupos de Linfocitos T / Proteínas de Unión al GTP Límite: Animals Idioma: En Revista: Sci Rep Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Subgrupos de Linfocitos T / Proteínas de Unión al GTP Límite: Animals Idioma: En Revista: Sci Rep Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido