title: IL-7-Induced Glycerol Transport and TAG Synthesis Promotes Memory CD8+ T Cell Longevity.
abstract: Memory T cells are critical for long-term immunity against reinfection and require interleukin-7 (IL-7), but the mechanisms by which IL-7 controls memory T cell survival, particularly metabolic fitness, remain elusive. We discover that IL-7 induces expression of the glycerol channel aquaporin 9 (AQP9) in virus-specific memory CD8+ T cells, but not naive cells, and that AQP9 is vitally required for their long-term survival. AQP9 deficiency impairs glycerol import into memory CD8+ T cells for fatty acid esterification and triglyceride (TAG) synthesis and storage. These defects can be rescued by ectopic expression of TAG synthases, which restores lipid stores and memory T cell survival. Finally, we find that TAG synthesis is a central component of IL-7-mediated survival of human and mouse memory CD8+T cells. This study uncovers the metabolic mechanisms by which IL-7 tailors the metabolism of memory T cells to promote their longevity and fast response to rechallenge.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Cui
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Staron
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Gray
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Ping-Chih
authors.initials: PC
authors.lastname: Ho
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815-6789, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Amezquita
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Jingxia
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815-6789, USA. Electronic address: susan.kaech@yale.edu.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Kaech
mesh_terms: D000818:Animals; D020346:Aquaporins / Q000378:metabolism; D001117:Arenaviridae Infections / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002470:Cell Survival; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D015851:Interleukin-7 / Q000378:metabolism; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology; D051379:Mice; D015398:Signal Transduction; D014280:Triglycerides / Q000378:metabolism*
chemical_list: C491638:Aqp9 protein, mouse; D020346:Aquaporins; D015851:Interleukin-7; D014280:Triglycerides; D005990:Glycerol