Journal article

Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway

Hassen Kared, Shu Wen Tan, Mai Chan Lau, Marion Chevrier, Crystal Tan, Wilson How, Glenn Wong, Marie Strickland, Benoit Malleret, Amanda Amoah, Karolina Pilipow, Veronica Zanon, Naomi Mc Govern, Josephine Lum, Jin Miao Chen, Bernett Lee, Maria Carolina Florian, Hartmut Geiger, Florent Ginhoux, Ezequiel Ruiz-Mateos Show all

Nature Communications | NATURE PUBLISHING GROUP | Published : 2020

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/β-catenin signature in CD4 TSCM and systemic increase in the levels of Dickkopf-related protein 1, a natural inhibitor of th..

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University of Melbourne Researchers

Grants

Awarded by BMRC


Awarded by BMRC transition fund


Awarded by Agency for Science, Technology and Research


Awarded by European Research Council


Awarded by High Impact Research/Ministry of Higher Education Research Grant, Malaysia (HIR/MOHE)


Awarded by Consejeria de Salud y Bienestar Social of Junta de Andalucia through the Nicolas Monardes Program


Awarded by Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III, Fondos Europeos para el Desarrollo Regional, FEDER


Awarded by Red de Investigacion en SIDA


Awarded by RU grant


Funding Acknowledgements

We thank Ivy Low (Flow Cytometry Platform), Esther Mok (Multiplex Analysis Platform), Alicia Seok Wei Tay, and Foo Shihui (Genomic Platform) from SIgN Immunomonitoring Platform (BMRC IAF 311006 grant and BMRC transition funds #H16/99/b0/011). We thank BD Biosciences and BioMarketing Services (BMS) for the generous loan of a BD FACS celesta at University of Malaya. We would like to acknowledge Dr. Robert Balderas (BD Biosciences) for his input in antibody panel design and high-dimensional flow cytometry experiments. We thank Dr. Etienne Becht and Dr. Evan W. Newell for the customized t-SNE and UMAP scripts for flow cytometry unbiased analysis. We thank Dr. Petronela Ancuta (University of Montreal) and Dr. Laurent Reina (SIgN) for the critical reading of the paper. The study is supported by a research grant from the Agency for Science, Technology and Research (No. 10-036), by the Singapore Immunology Network and by a Starting Grant from the European Research Council (ERC-StG-2014 PERSYST 640511 to E.L.). A.L. is a scholar of International Society for Advancement of Cytometry (ISAC). R.R. and A.K. are funded by the High Impact Research/Ministry of Higher Education Research Grant, Malaysia (HIR/MOHE; H-20001-E000001) and the RU grant (UMRG RP029-14HTM). E.R-M was supported by Consejeria de Salud y Bienestar Social of Junta de Andalucia through the Nicolas Monardes Program (C-0032/17) and Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III, Fondos Europeos para el Desarrollo Regional, FEDER, grants PI16/00684, PI19/01127, RETICS, Red de Investigacion en SIDA (RD16/0025/0020).