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

Author

Listed:
  • Hassen Kared

    (Agency for Science Technology and Research (A*STAR))

  • Shu Wen Tan

    (Agency for Science Technology and Research (A*STAR))

  • Mai Chan Lau

    (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)
    University of Southampton)

  • Benoit Malleret

    (Agency for Science Technology and Research (A*STAR)
    National University of Singapore)

  • 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
    Experimental Hematology and Cancer Biology, CCHMC)

  • 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
    University of Melbourne
    University of Malaya)

  • Adeeba Kamarulzaman

    (University of Malaya
    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)
    National University of Singapore
    University of Sherbrooke)

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.

Suggested Citation

  • 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 G, 2020. "Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14442-6
    DOI: 10.1038/s41467-020-14442-6
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    Cited by:

    1. Mingyang Ren & Sanguo Zhang & Qingzhao Zhang & Shuangge Ma, 2022. "Gaussian graphical model‐based heterogeneity analysis via penalized fusion," Biometrics, The International Biometric Society, vol. 78(2), pages 524-535, June.

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