RT Journal Article
T1 Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway
A1 Kared, Hassen
A1 Tan, Shu Wen
A1 Lau, Mai Chan
A1 Chevrier, Marion
A1 Tan, Crystal
A1 How, Wilson
A1 Wong, Glenn
A1 Strickland, Marie
A1 Malleret, Benoit
A1 Amoah, Amanda
A1 Pilipow, Karolina
A1 Zanon, Veronica
A1 Govern, Naomi Mc
A1 Lum, Josephine
A1 Chen, Jin Miao
A1 Lee, Bernett
A1 Florian, Maria Carolina
A1 Geiger, Hartmut
A1 Ginhoux, Florent
A1 Ruiz-Mateos, Ezequiel
A1 Fulop, Tamas
A1 Rajasuriar, Reena
A1 Kamarulzaman, Adeeba
A1 Ng, Tze Pin
A1 Lugli, Enrico
A1 Larbi, Anis
K1 Memory T cells
K1 Wnt signaling pathway
K1 Flow cytometry
K1 Immune system
K1 Catenins
K1 Células T de memoria
K1 Vía de señalización wnt
K1 Citometría de flujo
K1 Sistema inmunológico
K1 Cateninas
AB 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.
PB Springer Nature
YR 2020
FD 2020-02-10
LK http://hdl.handle.net/10668/3859
UL http://hdl.handle.net/10668/3859
LA en
NO Kared H, Tan SW, Lau MC, Chevrier M, Tan C, How W, et al. Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway. Nat Commun. 2020 Feb 10;11(1):821
DS RISalud
RD Apr 11, 2025