Maternal trans-vaccenic acid shapes neonatal T cell development and early-life immune imprinting
- Hao Fan
- Zhong Zheng
- Kaitlyn Oliphant
- Jiacheng Li
- Ryan Mack
- Cheng-Wei Ju
- Brandon Trandai
- Jiayi Tu
- Freya Q. Zhang
- Rukang Zhang
- Zhicheng Xie
- Chunzhao Yin
- Chufan Cai
- Megan S. Kennedy
- Tess McNeely
- Candace Cham
- Hardik Shah
- Lei Dong
- Rui Su
- Camilia R. Martin
- Brian T. Layden
- Robert B. Hamanaka
- Gökhan M. Mutlu
- Eugene B. Chang
- Jiwang Zhang
- Hongbo Chi
- Erika C. Claud
- Chuan He
- Jing Chen
2026-06-18
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 + ) T cell population and enhanced adaptive immunity against infection. TVA reprogrammed neonatal naïve CD4 + 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.