| Literature DB >> 32041953 |
Hassen Kared1, Shu Wen Tan2, Mai Chan Lau2, Marion Chevrier2, Crystal Tan2, Wilson How2, Glenn Wong2, Marie Strickland2,3, Benoit Malleret2,4, Amanda Amoah5, Karolina Pilipow6, Veronica Zanon6, Naomi Mc Govern2, Josephine Lum2, Jin Miao Chen2, Bernett Lee2, Maria Carolina Florian5, Hartmut Geiger5,7, Florent Ginhoux2, Ezequiel Ruiz-Mateos8, Tamas Fulop9, Reena Rajasuriar10,11,12, Adeeba Kamarulzaman10,12, Tze Pin Ng13, Enrico Lugli6, Anis Larbi14,15,16.
Abstract
The diversity of the naïve 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 (TSCM) contribute to such attrition is still unclear. Using single cells RNA sequencing and high-dimensional flow cytometry, we demonstrate that TSCM heterogeneity results from differential engagement of Wnt signaling. In humans, aging is associated with the coupled loss of Wnt/β-catenin signature in CD4 TSCM and systemic increase in the levels of Dickkopf-related protein 1, a natural inhibitor of the Wnt/β-catenin pathway. Functional assays support recent thymic emigrants as the precursors of CD4 TSCM. Our data thus hint that reversing TSCM defects by metabolic targeting of the Wnt/β-catenin pathway may be a viable approach to restore and preserve immune homeostasis in the context of immunological history.Entities:
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Year: 2020 PMID： 32041953 PMCID： PMC7010798 DOI： 10.1038/s41467-020-14442-6
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919