1. Age-associated impairment of T cell immunity is linked to sex-dimorphic elevation of N-glycan branching.
- Author
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Mkhikian, Haik, Hayama, Ken L, Khachikyan, Khachik, Li, Carey, Zhou, Raymond W, Pawling, Judy, Klaus, Suzi, Tran, Phuong QN, Ly, Kim M, Gong, Andrew D, Saryan, Hayk, Hai, Jasper L, Grigoryan, David, Lee, Philip L, Newton, Barbara L, Raffatellu, Manuela, Dennis, James W, and Demetriou, Michael
- Subjects
Immunosenescence ,N-acetyglucosamine ,N-glycan branching ,N-glycosylation ,T cell ,infection ,aging ,immunity ,interleukin-7 ,Aging ,Emerging Infectious Diseases ,Infectious Diseases ,Biodefense ,Prevention ,Vaccine Related ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being - Abstract
Impaired T cell immunity with aging increases mortality from infectious disease. The branching of Asparagine-linked glycans is a critical negative regulator of T cell immunity. Here we show that branching increases with age in females more than males, in naïve more than memory T cells, and in CD4+ more than CD8+ T cells. Female sex hormones and thymic output of naïve T cells (TN) decrease with age, however neither thymectomy nor ovariectomy altered branching. Interleukin-7 (IL-7) signaling was increased in old female more than male mouse TN cells, and triggered increased branching. N-acetylglucosamine, a rate-limiting metabolite for branching, increased with age in humans and synergized with IL-7 to raise branching. Reversing elevated branching rejuvenated T cell function and reduced severity of Salmonella infection in old female mice. These data suggest sex-dimorphic antagonistic pleiotropy, where IL-7 initially benefits immunity through TN maintenance but inhibits TN function by raising branching synergistically with age-dependent increases in N-acetylglucosamine.
- Published
- 2022