Maternal trans-vaccenic acid shapes neonatal T cell development and early-life immune imprinting.

Fan, Hao; Zheng, Zhong; Oliphant, Kaitlyn; Li, Jiacheng; Mack, Ryan; Ju, Cheng-Wei; Trandai, Brandon; Tu, Jiayi et al. · Science · 2026

basic_science · Level V

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Abstract

How maternal nutrition influences neonatal immune development and imprinting through breastfeeding remains largely unclear. We report that maternal supplementation with trans-vaccenic acid (TVA), the predominant naturally occurring trans-fatty acid in human breast milk, promoted neonatal T cell development in mice. Neonates fed by mothers on a TVA-enriched diet showed an expanded naïve cluster of differentiation 4 (CD4<sup>+</sup>) T cell population and enhanced adaptive immunity against infection. TVA reprogrammed neonatal naïve CD4<sup>+</sup> T cells through a G protein-coupled receptor-CCCTC-binding factor axis and promoted T helper cells (Th1)-skewing by cooperating with the transcription factor TBX21. Early-life exposure to maternal TVA via breastfeeding supported long-lasting antiviral immunity in adulthood. Our findings establish the multifaceted benefits of maternal nutrition and breastfeeding via TVA in promoting infant immune homeostasis and protective immunity.

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