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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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