Details

Autor(en) / Beteiligte

• 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

Titel

Age-associated impairment of T cell immunity is linked to sex-dimorphic elevation of N-glycan branching

Ist Teil von

• Nature aging, 2022-03, Vol.2 (3), p.231-242

Ort / Verlag

United States

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 (T ) decrease with age, however neither thymectomy nor ovariectomy altered branching. Interleukin-7 (IL-7) signaling was increased in old female more than male mouse T 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 infection in old female mice. These data suggest sex-dimorphic antagonistic pleiotropy, where IL-7 initially benefits immunity through T maintenance but inhibits T function by raising branching synergistically with age-dependent increases in N-acetylglucosamine.