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Age-associated impairment of T cell immunity is linked to sex-dimorphic elevation of N-glycan branching.
Mkhikian, Haik; Hayama, Ken L; Khachikyan, Khachik; Li, Carey; Zhou, Raymond W; Pawling, Judy; Klaus, Suzi; Tran, Phuong Q N; Ly, Kim M; Gong, Andrew D; Saryan, Hayk; Hai, Jasper L; Grigoryan, David; Lee, Philip L; Newton, Barbara L; Raffatellu, Manuela; Dennis, James W; Demetriou, Michael.
Affiliation
  • Mkhikian H; Department of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA, USA.
  • Hayama KL; Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA, USA.
  • Khachikyan K; Department of Neurology, University of California, Irvine, Irvine, CA, USA.
  • Li C; Department of Neurology, University of California, Irvine, Irvine, CA, USA.
  • Zhou RW; Department of Neurology, University of California, Irvine, Irvine, CA, USA.
  • Pawling J; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
  • Klaus S; Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA, USA.
  • Tran PQN; Department of Neurology, University of California, Irvine, Irvine, CA, USA.
  • Ly KM; Department of Neurology, University of California, Irvine, Irvine, CA, USA.
  • Gong AD; Department of Neurology, University of California, Irvine, Irvine, CA, USA.
  • Saryan H; Department of Neurology, University of California, Irvine, Irvine, CA, USA.
  • Hai JL; Department of Neurology, University of California, Irvine, Irvine, CA, USA.
  • Grigoryan D; Department of Neurology, University of California, Irvine, Irvine, CA, USA.
  • Lee PL; Department of Neurology, University of California, Irvine, Irvine, CA, USA.
  • Newton BL; Department of Neurology, University of California, Irvine, Irvine, CA, USA.
  • Raffatellu M; Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA, USA.
  • Dennis JW; Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
  • Demetriou M; Center for Mucosal Immunology, Allergy, and Vaccines, Chiba University-UC San Diego, La Jolla, CA, USA.
Nat Aging ; 2(3): 231-242, 2022 03.
Article in En | MEDLINE | ID: mdl-35528547
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Acetylglucosamine / CD8-Positive T-Lymphocytes Type of study: Risk_factors_studies Limits: Animals / Female / Humans / Male Language: En Journal: Nat Aging Year: 2022 Document type: Article Affiliation country: United States
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Acetylglucosamine / CD8-Positive T-Lymphocytes Type of study: Risk_factors_studies Limits: Animals / Female / Humans / Male Language: En Journal: Nat Aging Year: 2022 Document type: Article Affiliation country: United States