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- W4366162595 abstract "Chronic systemic inflammation is one of the hallmarks of the aging immune system. Here we show that activated T cells from older adults contribute to inflammaging by releasing mitochondrial DNA (mtDNA) into their environment due to an increased expression of the cytokine-inducible SH2-containing protein (CISH). CISH targets ATP6V1A, an essential component of the proton pump V-ATPase, for proteasomal degradation, thereby impairing lysosomal function. Impaired lysosomal activity caused intracellular accumulation of multivesicular bodies and amphisomes and the export of their cargos, including mtDNA. CISH silencing in T cells from older adults restored lysosomal activity and prevented amphisomal release. In antigen-specific responses in vivo, CISH-deficient CD4+ T cells released less mtDNA and induced fewer inflammatory cytokines. Attenuating CISH expression may present a promising strategy to reduce inflammation in an immune response of older individuals." @default.
- W4366162595 created "2023-04-19" @default.
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- W4366162595 date "2023-04-17" @default.
- W4366162595 modified "2023-10-14" @default.
- W4366162595 title "CISH impairs lysosomal function in activated T cells resulting in mitochondrial DNA release and inflammaging" @default.
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- W4366162595 doi "https://doi.org/10.1038/s43587-023-00399-w" @default.
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