Nature communications · 2020
Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Ошибки и ограничения
История · было → стало
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Kared Hassen, Tan Shu Wen, Lau Mai Chan, Chevrier Marion, Tan Crystal, How Wilson, Wong Glenn, Strickland Marie, Malleret Benoit, Amoah Amanda, Pilipow Karolina, Zanon Veronica, Govern Naomi Mc, Lum Josephine, Chen Jin Miao, Lee Bernett, Florian Maria Carolina, Geiger Hartmut, Ginhoux Florent, Ruiz-Mateos Ezequiel, Fulop Tamas, Rajasuriar Reena, Kamarulzaman Adeeba, Ng Tze Pin, Lugli Enrico, Larbi Anis
Аннотация
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.