MiR-29a/b Suppresses CD8+ T Cell Effector Function and Intestinal Inflammation

  • Exploration (Beijing). 2025 Jun 10;5(4):20240363. doi: 10.1002/EXP.20240363.
Yingying Lin  1  2 ,  Yuqi Wang  1 ,  Yuning Zhang  1 ,  Yao Lu  1 ,  Juan Chen  2 ,  Yongting Luo  2 ,  Jian He  3 ,  Qingfeng Luo  4 ,  Heng Quan  2 ,  Weiru Yu  2 ,  Yujia Luo  2 ,  Peng Xue  1 ,  Yi Xue  2 ,  Xiaoya Lin  2 ,  Rui Ding  2 ,  Lining Chen  1 ,  Yiran Wang  2 ,  Zenghui Xia  1 ,  Liang Zhao  1 ,  Hao Zhang  1 ,  Ran Wang  2 ,  Qingyu Wang  2 ,  Xifan Wang  5 ,  Jiaqi Su  6 ,  Fazheng Ren  2 ,  Cong Lv  2 ,  Yixuan Li  2 ,  Huiyuan Guo  1  2  3
Affiliations
  • 1. College of Food Science and Nutritional Engineering China Agricultural University Beijing China.
  • 2. Key Laboratory of Functional Dairy, Department of Nutrition and Health China Agricultural University Beijing China.
  • 3. Nutrition and Health Research Center National Center of Technology Innovation for Dairy Hohhot China.
  • 4. Department of Gastroenterology, Beijing Hospital, National Center of Gerontology Institute of Geriatric Medicine, Chinese Academy of Medical Science Beijing China.
  • 5. Department of Obstetrics and Gynecology Columbia University New York New York USA.
  • 6. Department of Health Sciences and Technology ETH Zurich Zurich Switzerland.
PMID: 40873647 DOI: 10.1002/EXP.20240363
Abstract

The role of CD8+ T cells in the pathogenesis of ulcerative colitis (UC) remains unclear. Similarly, the posttranscriptional regulation of the highly heterogenic CD8+ T cell populations and their effector function in IBD also remains poorly understood. Here, we find that miR-29a and -29b (miR-29a/b) regulate T cell fate, and their expression is higher near damaged colon tissue in patients with IBD compared to controls. In mice, we find that miR-29a/b suppresses the differentiation of CD8+ T cells and the secretion of pro-inflammatory and chemotactic factors during severe colitis by inhibiting transcriptional pathways, including those involving the T cell receptor and JAK-STAT signaling. Furthermore, we identify Ifng, an inflammatory factor that drives immune response and the reshaping of CD8+ T cell fate, as a potential target of the miRNAs. Finally, we show that delivery of miR-29 mimics to the colon of mice is sufficient to alleviate DSS-induced inflammation. Together, these data show that miR-29 plays an important role in suppressing T cell overactivation during inflammatory diseases.

Keywords
CD8+ T cell; Ifng‐JAK‐STAT; differentiation; miR‐29a/b; ulcerative colitis.
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