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

Hassen Kared (), Shu Wen Tan, Jorge 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, Tamas Fulop, Reena Rajasuriar, Adeeba Kamarulzaman, Tze Pin Ng, Enrico Lugli and Anis Larbi ()
Additional contact information
Hassen Kared: Agency for Science Technology and Research (A*STAR)
Shu Wen Tan: Agency for Science Technology and Research (A*STAR)
Marion Chevrier: Agency for Science Technology and Research (A*STAR)
Crystal Tan: Agency for Science Technology and Research (A*STAR)
Wilson How: Agency for Science Technology and Research (A*STAR)
Glenn Wong: Agency for Science Technology and Research (A*STAR)
Marie Strickland: Agency for Science Technology and Research (A*STAR)
Benoit Malleret: Agency for Science Technology and Research (A*STAR)
Amanda Amoah: University of Ulm
Karolina Pilipow: Laboratory of Translational Immunology (LTI)
Veronica Zanon: Laboratory of Translational Immunology (LTI)
Naomi Mc Govern: Agency for Science Technology and Research (A*STAR)
Josephine Lum: Agency for Science Technology and Research (A*STAR)
Jin Miao Chen: Agency for Science Technology and Research (A*STAR)
Bernett Lee: Agency for Science Technology and Research (A*STAR)
Maria Carolina Florian: University of Ulm
Hartmut Geiger: University of Ulm
Florent Ginhoux: Agency for Science Technology and Research (A*STAR)
Ezequiel Ruiz-Mateos: University of Seville
Tamas Fulop: University of Sherbrooke
Reena Rajasuriar: University of Malaya
Adeeba Kamarulzaman: University of Malaya
Tze Pin Ng: National University of Singapore
Enrico Lugli: Laboratory of Translational Immunology (LTI)
Anis Larbi: Agency for Science Technology and Research (A*STAR)

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: 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 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.

Date: 2020
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DOI: 10.1038/s41467-020-14442-6

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