CD38 expression by neonatal human naive CD4+ T cells shapes their distinct metabolic and tolerogenic properties.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41746743.
- Also identified by DOI 10.1172/JCI200062 and PMC identifier 13078883.
- 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
Neonatal life is marked by rapid antigen exposure, necessitating establishment of peripheral immune tolerance via conversion of naive CD4+ T cells into Tregs. We demonstrated heightened capacity for FOXP3 expression and tolerogenic function among cord blood versus adult blood naive CD4+ T cells. Further, this was linked to a distinct cord blood metabolic profile and elevated neonatal expression of the NADase, CD38. Early-life naive CD4+ T cells demonstrated a metabolic preference for glycolysis, which directly facilitated their differentiation trajectory. We revealed an age-dependent gradient in CD38 levels on naive CD4+ T cells and showed that high CD38 expression contributes to the glycolytic state and tolerogenic potential of neonatal CD4+ T cells, effects mediated at least partly 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 naive CD4+ compartment.
Medical subject headings
- ADP-ribosyl Cyclase 1
- CD4-Positive T-Lymphocytes
- Immune Tolerance
- Membrane Glycoproteins