Maternal trans-vaccenic acid shapes neonatal T cell development and early-life immune imprinting
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.
Authors
- Chufan Cai (ORCID: https://orcid.org/0000-0001-6209-0820)
- Candace M. Cham (ORCID: https://orcid.org/0000-0001-7135-949X)
- Megan S Kennedy (ORCID: https://orcid.org/0000-0001-6472-2182)
- Cheng‐Wei Ju (ORCID: https://orcid.org/0000-0002-2250-8548)
- Erika C. Claud (ORCID: https://orcid.org/0000-0002-2408-2114)
- Ryan Mack (ORCID: https://orcid.org/0000-0001-8133-0594)
- Zhicheng Xie (ORCID: https://orcid.org/0009-0003-3990-0508)
- Jiacheng Li (ORCID: https://orcid.org/0000-0003-3730-3534)
- Kaitlyn Oliphant (ORCID: https://orcid.org/0000-0002-6921-7094)
- Eugene B. Chang (ORCID: https://orcid.org/0000-0001-5972-8248)
- Freya Q. Zhang (ORCID: https://orcid.org/0000-0002-2596-0433)
- Hao Fan (ORCID: https://orcid.org/0000-0001-5245-9698)
- Jiayi Tu (ORCID: https://orcid.org/0000-0002-2626-0084)
- Hardik Shah (ORCID: https://orcid.org/0000-0001-8408-5686)
- Camilia R. Martin (ORCID: https://orcid.org/0000-0003-2783-6126)
- Gökhan M. Mutlu (ORCID: https://orcid.org/0000-0002-2056-612X)
- Robert B. Hamanaka (ORCID: https://orcid.org/0000-0002-8909-356X)
- Lei Dong (ORCID: https://orcid.org/0000-0001-9574-0148)
- Hongbo Chi (ORCID: https://orcid.org/0000-0002-9997-2496)
- Rukang Zhang (ORCID: https://orcid.org/0000-0001-9554-4999)
- Chuan He (ORCID: https://orcid.org/0000-0003-4319-7424)
- Jing Chen (ORCID: https://orcid.org/0000-0002-5376-9062)
- Rui Su (ORCID: https://orcid.org/0000-0002-4807-6229)
- Zhong Zheng (ORCID: https://orcid.org/0000-0001-8194-115X)
- Jiwang Zhang (ORCID: https://orcid.org/0000-0003-4309-2892)
- Chunzhao Yin
- Brandon Trandai
- Brian T. Layden
- Tess McNeely (ORCID: https://orcid.org/0009-0002-4274-6022)
Institutions
- St. Jude Children's Research Hospital (US)
- Loyola University Chicago (US)
- Cornell University (US)
- University of Illinois Chicago (US)
- University of Chicago (US)
- City of Hope (US)
- Weill Cornell Medicine (US)
- Beckman Research Institute
- The University of Texas Southwestern Medical Center (US)
Publication Details
- Journal
- Science
- Published
- 2026-06-18
- DOI
- https://doi.org/10.1126/science.aea4041
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 0.00