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Article Abstract
Neonatal life is marked by rapid antigen exposure, necessitating establishment of peripheral immune tolerance via conversion of naïve CD4 T cells into regulatory T cells (Tregs). Here, we demonstrate heighted capacity for FOXP3 expression and tolerogenic function among cord blood versus adult blood naive CD4 T cells and that this is linked to their unique metabolic profile and elevated expression of the NADase, CD38. Early life naïve CD4 T cells demonstrate a metabolic preference for glycolysis, which directly facilitates their differentiation trajectory. We reveal an age-dependent gradient in CD38 levels on naïve CD4 T cells and show that high CD38 expression contributes to both the glycolytic state and tolerogenic potential of neonatal CD4 T cells, effects that are mediated at least in part via the NAD-dependent deacetylase SIRT1. Thus, the early life window for peripheral tolerance in humans is critically enabled by the immunometabolic state of the naïve CD4 compartment.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12262530 | PMC |
| http://dx.doi.org/10.1101/2025.01.02.631038 | DOI Listing |
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