期刊
NATURE COMMUNICATIONS
卷 11, 期 1, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-020-14442-6
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资金
- BMRC [IAF 311006]
- BMRC transition fund [H16/99/b0/011]
- Agency for Science, Technology and Research [10-036]
- Singapore Immunology Network
- European Research Council [ERC-StG-2014 PERSYST 640511]
- High Impact Research/Ministry of Higher Education Research Grant, Malaysia (HIR/MOHE) [H-20001-E000001]
- Consejeria de Salud y Bienestar Social of Junta de Andalucia through the Nicolas Monardes Program [C-0032/17]
- Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III, Fondos Europeos para el Desarrollo Regional, FEDER [PI16/00684, PI19/01127]
- RETICS
- Red de Investigacion en SIDA [RD16/0025/0020]
- RU grant [UMRG RP029-14HTM]
The diversity of the naive T cell repertoire drives the replenishment potential and capacity of memory T cells to respond to immune challenges. Attrition of the immune system is associated with an increased prevalence of pathologies in aged individuals, but whether stem cell memory T lymphocytes (T-SCM) contribute to such attrition is still unclear. Using single cells RNA sequencing and high-dimensional flow cytometry, we demonstrate that T-SCM heterogeneity results from differential engagement of Wnt signaling. In humans, aging is associated with the coupled loss of Wnt/beta-catenin signature in CD4 T-SCM and systemic increase in the levels of Dickkopf-related protein 1, a natural inhibitor of the Wnt/beta-catenin pathway. Functional assays support recent thymic emigrants as the precursors of CD4 T-SCM. Our data thus hint that reversing T-SCM defects by metabolic targeting of the Wnt/beta-catenin pathway may be a viable approach to restore and preserve immune homeostasis in the context of immunological history.
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