Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32041953.
- Also identified by DOI 10.1038/s41467-020-14442-6 and PMC identifier 7010798.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 (T<sub>SCM</sub>) contribute to such attrition is still unclear. Using single cells RNA sequencing and high-dimensional flow cytometry, we demonstrate that T<sub>SCM</sub> heterogeneity results from differential engagement of Wnt signaling. In humans, aging is associated with the coupled loss of Wnt/β-catenin signature in CD4 T<sub>SCM</sub> 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 T<sub>SCM</sub>. Our data thus hint that reversing T<sub>SCM</sub> 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.
Medical subject headings
- CD4-Positive T-Lymphocytes
- Precursor Cells, T-Lymphoid
- Wnt Signaling Pathway