Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-020-14442-6
Title: Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway
Authors: Kared, H.
Tan, S.W.
Lau, M.C.
Chevrier, M.
Tan, C.
How, W.
Wong, G.
Strickland, M.
Malleret, B. 
Amoah, A.
Pilipow, K.
Zanon, V.
Govern, N.M.
Lum, J.
Chen, J.M.
Lee, B.
Florian, M.C.
Geiger, H.
Ginhoux, F.
Ruiz-Mateos, E.
Fulop, T.
Rajasuriar, R.
Kamarulzaman, A.
Ng, T.P. 
Lugli, E.
Larbi, A. 
Issue Date: 2020
Publisher: Nature Research
Citation: Kared, H., Tan, S.W., Lau, M.C., Chevrier, M., Tan, C., How, W., Wong, G., Strickland, M., Malleret, B., Amoah, A., Pilipow, K., Zanon, V., Govern, N.M., Lum, J., Chen, J.M., Lee, B., Florian, M.C., Geiger, H., Ginhoux, F., Ruiz-Mateos, E., Fulop, T., Rajasuriar, R., Kamarulzaman, A., Ng, T.P., Lugli, E., Larbi, A. (2020). Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway. Nature Communications 11 (1) : 821. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-020-14442-6
Rights: Attribution 4.0 International
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/?-catenin signature in CD4 TSCM and systemic increase in the levels of Dickkopf-related protein 1, a natural inhibitor of the Wnt/?-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/?-catenin pathway may be a viable approach to restore and preserve immune homeostasis in the context of immunological history. © 2020, The Author(s).
Source Title: Nature Communications
URI: https://scholarbank.nus.edu.sg/handle/10635/198123
ISSN: 2041-1723
DOI: 10.1038/s41467-020-14442-6
Rights: Attribution 4.0 International
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