母乳中の栄養素がマウスの免疫系発達を促進することを解明(Nutrient in breast milk helps boosts immune system development in mice)

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2026-06-22 シカゴ大学(UChicago)

University of Chicagoの研究チームは、母乳中に最も多く含まれるトランス脂肪酸であるトランスバクセン酸(Trans-vaccenic acid:TVA)が、新生児期の免疫系の発達を促進し、その効果が離乳後も長期間維持されることをマウス実験で明らかにした。研究では、授乳期にTVAを摂取したマウスは、胸腺におけるT細胞の成熟や免疫細胞の発達が促進され、成長後も感染防御能力や免疫応答が向上していた。一方、TVAを十分に摂取できなかったマウスでは免疫系の成熟が不十分となり、長期的な免疫機能にも影響が及んだ。TVAは反芻動物由来の乳製品などにも含まれる天然由来のトランス脂肪酸であり、工業的トランス脂肪酸とは性質が異なる。本研究は、母乳中の特定栄養成分が乳児の免疫系を長期にわたり形成する重要な役割を担うことを示し、乳児栄養や人工乳の改良、免疫機能の発達機構の解明につながる新たな知見を提供した。

<関連情報>

母体由来のトランスバクセン酸が新生児のT細胞発達と生後早期の免疫インプリンティングを形成する Maternal trans-vaccenic acid shapes neonatal T cell development and early-life immune imprinting

Hao Fan, Zhong Zheng, Kaitlyn Oliphant, Jiacheng Li, […] , and Jing Chen
Science  Published:18 Jun 2026
DOI:https://doi.org/10.1126/science.aea4041

母乳中の栄養素がマウスの免疫系発達を促進することを解明(Nutrient in breast milk helps boosts immune system development in mice)
Maternal trans-vaccenic acid (TVA) in breast milk programs neonatal T cell development and immune imprinting.

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.

 

トランスバクセン酸はCD8 + T細胞と抗腫瘍免疫を再プログラムする Trans-vaccenic acid reprograms CD8+ T cells and anti-tumour immunity

Hao Fan,Siyuan Xia,Junhong Xiang,Yuancheng Li,Matthew O. Ross,Seon Ah Lim,Fan Yang,Jiayi Tu,Lishi Xie,Urszula Dougherty,Freya Q. Zhang,Zhong Zheng,Rukang Zhang,Rong Wu,Lei Dong,Rui Su,Xiufen Chen,Thomas Althaus,Peter A. Riedell,Patrick B. Jonker,Alexander Muir,Gregory B. Lesinski,Sarwish Rafiq,Madhav V. Dhodapkar,… Jing Chen
Nature  Published:22 November 2023
DOI:https://doi.org/10.1038/s41586-023-06749-3

Abstract

Diet-derived nutrients are inextricably linked to human physiology by providing energy and biosynthetic building blocks and by functioning as regulatory molecules. However, the mechanisms by which circulating nutrients in the human body influence specific physiological processes remain largely unknown. Here we use a blood nutrient compound library-based screening approach to demonstrate that dietary trans-vaccenic acid (TVA) directly promotes effector CD8+ T cell function and anti-tumour immunity in vivo. TVA is the predominant form of trans-fatty acids enriched in human milk, but the human body cannot produce TVA endogenously1. Circulating TVA in humans is mainly from ruminant-derived foods including beef, lamb and dairy products such as milk and butter2,3, but only around 19% or 12% of dietary TVA is converted to rumenic acid by humans or mice, respectively4,5. Mechanistically, TVA inactivates the cell-surface receptor GPR43, an immunomodulatory G protein-coupled receptor activated by its short-chain fatty acid ligands6,7,8. TVA thus antagonizes the short-chain fatty acid agonists of GPR43, leading to activation of the cAMP–PKA–CREB axis for enhanced CD8+ T cell function. These findings reveal that diet-derived TVA represents a mechanism for host-extrinsic reprogramming of CD8+ T cells as opposed to the intrahost gut microbiota-derived short-chain fatty acids. TVA thus has translational potential for the treatment of tumours.

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