TY - JOUR
T1 - Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway
AU - Kared, Hassen
AU - Tan, Shu Wen
AU - Lau, Mai Chan
AU - Chevrier, Marion
AU - Tan, Crystal
AU - How, Wilson
AU - Wong, Glenn
AU - Strickland, Marie
AU - Malleret, Benoit
AU - Amoah, Amanda
AU - Pilipow, Karolina
AU - Zanon, Veronica
AU - Govern, Naomi Mc
AU - Lum, Josephine
AU - Chen, Jin Miao
AU - Lee, Bernett
AU - Florian, Maria Carolina
AU - Geiger, Hartmut
AU - Ginhoux, Florent
AU - Ruiz-Mateos, Ezequiel
AU - Fulop, Tamas
AU - Rajasuriar, Reena
AU - Kamarulzaman, Adeeba
AU - Ng, Tze Pin
AU - Lugli, Enrico
AU - Larbi, Anis
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85079242517&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-14442-6
DO - 10.1038/s41467-020-14442-6
M3 - Article
C2 - 32041953
AN - SCOPUS:85079242517
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 821
ER -