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

H Hao Fan (Department of Medicine, The University of Chicago, Chicago, IL, USA.) Z Zhong Zheng (Department of Chemistry, The University of Chicago, Chicago, IL, USA.) K Kaitlyn Oliphant (Department of Pediatrics, The University of Chicago, Chicago, IL, USA.) J Jiacheng Li (Department of Medicine, The University of Chicago, Chicago, IL, USA.) R Ryan Mack (Department of Cancer Biology, Loyola University Chicago, Maywood, IL, USA.) C Cheng-Wei Ju (Department of Chemistry, The University of Chicago, Chicago, IL, USA.) B Brandon Trandai (Department of Pediatrics, The University of Chicago, Chicago, IL, USA.) J Jiayi Tu F Freya Q. Zhang (Department of Medicine, The University of Chicago, Chicago, IL, USA.) R Rukang Zhang (Department of Medicine, The University of Chicago, Chicago, IL, USA.) Z Zhicheng Xie (Department of Medicine, The University of Chicago, Chicago, IL, USA.) C Chunzhao Yin (Department of Medicine, The University of Chicago, Chicago, IL, USA.) C Chufan Cai (Department of Medicine, The University of Chicago, Chicago, IL, USA.) M Megan S. Kennedy (Department of Medicine, The University of Chicago, Chicago, IL, USA.) T Tess McNeely (Department of Medicine, The University of Chicago, Chicago, IL, USA.) C Candace Cham (Department of Medicine, The University of Chicago, Chicago, IL, USA.) H Hardik Shah L Lei Dong (Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.) R Rui Su C Camilia R. Martin (Division of Neonatology, Weill Cornell Medicine, New York, NY, USA.) B Brian T. Layden (Department of Medicine, University of Illinois Chicago, Chicago, IL, USA.) R Robert B. Hamanaka (Department of Medicine, The University of Chicago, Chicago, IL, USA.) G Gökhan M. Mutlu (Department of Medicine, The University of Chicago, Chicago, IL, USA.) E Eugene B. Chang (Department of Medicine, The University of Chicago, Chicago, IL, USA.) J Jiwang Zhang (Department of Cancer Biology, Loyola University Chicago, Maywood, IL, USA.) H Hongbo Chi E Erika C. Claud (Department of Pediatrics, The University of Chicago, Chicago, IL, USA.) C Chuan He J Jing Chen

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 + ) 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.

Article Details

Journal Science
Volume / Issue Vol. 392, Issue 6804
Published June 18, 2026
ISSN 0036-8075
Publisher American Association for the Advancement of Science

Journal Info

Science

American Association for the Advancement of Science

ISSN: 0036-8075 Social Sciences

Authors (29)

H

Hao Fan

Department of Medicine, The University of Chicago, Chicago, IL, USA.

Z

Zhong Zheng

Department of Chemistry, The University of Chicago, Chicago, IL, USA.

K

Kaitlyn Oliphant

Department of Pediatrics, The University of Chicago, Chicago, IL, USA.

J

Jiacheng Li

Department of Medicine, The University of Chicago, Chicago, IL, USA.

R

Ryan Mack

Department of Cancer Biology, Loyola University Chicago, Maywood, IL, USA.

C

Cheng-Wei Ju

Department of Chemistry, The University of Chicago, Chicago, IL, USA.

B

Brandon Trandai

Department of Pediatrics, The University of Chicago, Chicago, IL, USA.

J

Jiayi Tu

F

Freya Q. Zhang

Department of Medicine, The University of Chicago, Chicago, IL, USA.

R

Rukang Zhang

Department of Medicine, The University of Chicago, Chicago, IL, USA.

Z

Zhicheng Xie

Department of Medicine, The University of Chicago, Chicago, IL, USA.

C

Chunzhao Yin

Department of Medicine, The University of Chicago, Chicago, IL, USA.

C

Chufan Cai

Department of Medicine, The University of Chicago, Chicago, IL, USA.

M

Megan S. Kennedy

Department of Medicine, The University of Chicago, Chicago, IL, USA.

T

Tess McNeely

Department of Medicine, The University of Chicago, Chicago, IL, USA.

C

Candace Cham

Department of Medicine, The University of Chicago, Chicago, IL, USA.

H

Hardik Shah

L

Lei Dong

Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.

R

Rui Su

C

Camilia R. Martin

Division of Neonatology, Weill Cornell Medicine, New York, NY, USA.

B

Brian T. Layden

Department of Medicine, University of Illinois Chicago, Chicago, IL, USA.

R

Robert B. Hamanaka

Department of Medicine, The University of Chicago, Chicago, IL, USA.

G

Gökhan M. Mutlu

Department of Medicine, The University of Chicago, Chicago, IL, USA.

E

Eugene B. Chang

Department of Medicine, The University of Chicago, Chicago, IL, USA.

J

Jiwang Zhang

Department of Cancer Biology, Loyola University Chicago, Maywood, IL, USA.

H

Hongbo Chi

E

Erika C. Claud

Department of Pediatrics, The University of Chicago, Chicago, IL, USA.

C

Chuan He

J

Jing Chen