%0 Journal Article
%A Kared, Hassen
%A Tan, Shu Wen
%A Lau, Mai Chan
%A Chevrier, Marion
%A Tan, Crystal
%A How, Wilson
%A Wong, Glenn
%A Strickland, Marie
%A Malleret, Benoit
%A Amoah, Amanda
%A Pilipow, Karolina
%A Zanon, Veronica
%A Govern, Naomi Mc
%A Lum, Josephine
%A Chen, Jin Miao
%A Lee, Bernett
%A Florian, Maria Carolina
%A Geiger, Hartmut
%A Ginhoux, Florent
%A Ruiz-Mateos, Ezequiel
%A Fulop, Tamas
%A Rajasuriar, Reena
%A Kamarulzaman, Adeeba
%A Ng, Tze Pin
%A Lugli, Enrico
%A Larbi, Anis
%T Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway
%D 2020
%U http://hdl.handle.net/10668/3859
%X 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.
%K Memory T cells
%K Wnt signaling pathway
%K Flow cytometry
%K Immune system
%K Catenins
%K Células T de memoria
%K Vía de señalización wnt
%K Citometría de flujo
%K Sistema inmunológico
%K Cateninas
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