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

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 (mi...

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Main Authors: Yingying Lin, Yuqi Wang, Yuning Zhang, Yao Lu, Juan Chen, Yongting Luo, Jian He, Qingfeng Luo, Heng Quan, Weiru Yu, Yujia Luo, Peng Xue, Yi Xue, Xiaoya Lin, Rui Ding, Lining Chen, Yiran Wang, Zenghui Xia, Liang Zhao, Hao Zhang, Ran Wang, Qingyu Wang, Xifan Wang, Jiaqi Su, Fazheng Ren, Cong Lv, Yixuan Li, Huiyuan Guo
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Exploration
Subjects:
Online Access:https://doi.org/10.1002/EXP.20240363
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author Yingying Lin
Yuqi Wang
Yuning Zhang
Yao Lu
Juan Chen
Yongting Luo
Jian He
Qingfeng Luo
Heng Quan
Weiru Yu
Yujia Luo
Peng Xue
Yi Xue
Xiaoya Lin
Rui Ding
Lining Chen
Yiran Wang
Zenghui Xia
Liang Zhao
Hao Zhang
Ran Wang
Qingyu Wang
Xifan Wang
Jiaqi Su
Fazheng Ren
Cong Lv
Yixuan Li
Huiyuan Guo
author_facet Yingying Lin
Yuqi Wang
Yuning Zhang
Yao Lu
Juan Chen
Yongting Luo
Jian He
Qingfeng Luo
Heng Quan
Weiru Yu
Yujia Luo
Peng Xue
Yi Xue
Xiaoya Lin
Rui Ding
Lining Chen
Yiran Wang
Zenghui Xia
Liang Zhao
Hao Zhang
Ran Wang
Qingyu Wang
Xifan Wang
Jiaqi Su
Fazheng Ren
Cong Lv
Yixuan Li
Huiyuan Guo
author_sort Yingying Lin
collection DOAJ
description 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.
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record_format Article
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spelling doaj-art-bdb45aa5f1424517ab489a41480a92b92025-08-26T10:32:53ZengWileyExploration2766-85092766-20982025-08-0154n/an/a10.1002/EXP.20240363MiR‐29a/b Suppresses CD8+ T Cell Effector Function and Intestinal InflammationYingying Lin0Yuqi Wang1Yuning Zhang2Yao Lu3Juan Chen4Yongting Luo5Jian He6Qingfeng Luo7Heng Quan8Weiru Yu9Yujia Luo10Peng Xue11Yi Xue12Xiaoya Lin13Rui Ding14Lining Chen15Yiran Wang16Zenghui Xia17Liang Zhao18Hao Zhang19Ran Wang20Qingyu Wang21Xifan Wang22Jiaqi Su23Fazheng Ren24Cong Lv25Yixuan Li26Huiyuan Guo27College of Food Science and Nutritional Engineering China Agricultural University Beijing ChinaCollege of Food Science and Nutritional Engineering China Agricultural University Beijing ChinaCollege of Food Science and Nutritional Engineering China Agricultural University Beijing ChinaCollege of Food Science and Nutritional Engineering China Agricultural University Beijing ChinaKey Laboratory of Functional Dairy, Department of Nutrition and Health China Agricultural University Beijing ChinaKey Laboratory of Functional Dairy, Department of Nutrition and Health China Agricultural University Beijing ChinaNutrition and Health Research Center National Center of Technology Innovation for Dairy Hohhot ChinaDepartment of Gastroenterology, Beijing Hospital, National Center of Gerontology Institute of Geriatric Medicine, Chinese Academy of Medical Science Beijing ChinaKey Laboratory of Functional Dairy, Department of Nutrition and Health China Agricultural University Beijing ChinaKey Laboratory of Functional Dairy, Department of Nutrition and Health China Agricultural University Beijing ChinaKey Laboratory of Functional Dairy, Department of Nutrition and Health China Agricultural University Beijing ChinaCollege of Food Science and Nutritional Engineering China Agricultural University Beijing ChinaKey Laboratory of Functional Dairy, Department of Nutrition and Health China Agricultural University Beijing ChinaKey Laboratory of Functional Dairy, Department of Nutrition and Health China Agricultural University Beijing ChinaKey Laboratory of Functional Dairy, Department of Nutrition and Health China Agricultural University Beijing ChinaCollege of Food Science and Nutritional Engineering China Agricultural University Beijing ChinaKey Laboratory of Functional Dairy, Department of Nutrition and Health China Agricultural University Beijing ChinaCollege of Food Science and Nutritional Engineering China Agricultural University Beijing ChinaCollege of Food Science and Nutritional Engineering China Agricultural University Beijing ChinaCollege of Food Science and Nutritional Engineering China Agricultural University Beijing ChinaKey Laboratory of Functional Dairy, Department of Nutrition and Health China Agricultural University Beijing ChinaKey Laboratory of Functional Dairy, Department of Nutrition and Health China Agricultural University Beijing ChinaDepartment of Obstetrics and Gynecology Columbia University New York New York USADepartment of Health Sciences and Technology ETH Zurich Zurich SwitzerlandKey Laboratory of Functional Dairy, Department of Nutrition and Health China Agricultural University Beijing ChinaKey Laboratory of Functional Dairy, Department of Nutrition and Health China Agricultural University Beijing ChinaKey Laboratory of Functional Dairy, Department of Nutrition and Health China Agricultural University Beijing ChinaCollege of Food Science and Nutritional Engineering China Agricultural University Beijing ChinaABSTRACT 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.https://doi.org/10.1002/EXP.20240363CD8+ T celldifferentiationIfng‐JAK‐STATmiR‐29a/bulcerative colitis
spellingShingle Yingying Lin
Yuqi Wang
Yuning Zhang
Yao Lu
Juan Chen
Yongting Luo
Jian He
Qingfeng Luo
Heng Quan
Weiru Yu
Yujia Luo
Peng Xue
Yi Xue
Xiaoya Lin
Rui Ding
Lining Chen
Yiran Wang
Zenghui Xia
Liang Zhao
Hao Zhang
Ran Wang
Qingyu Wang
Xifan Wang
Jiaqi Su
Fazheng Ren
Cong Lv
Yixuan Li
Huiyuan Guo
MiR‐29a/b Suppresses CD8+ T Cell Effector Function and Intestinal Inflammation
Exploration
CD8+ T cell
differentiation
Ifng‐JAK‐STAT
miR‐29a/b
ulcerative colitis
title MiR‐29a/b Suppresses CD8+ T Cell Effector Function and Intestinal Inflammation
title_full MiR‐29a/b Suppresses CD8+ T Cell Effector Function and Intestinal Inflammation
title_fullStr MiR‐29a/b Suppresses CD8+ T Cell Effector Function and Intestinal Inflammation
title_full_unstemmed MiR‐29a/b Suppresses CD8+ T Cell Effector Function and Intestinal Inflammation
title_short MiR‐29a/b Suppresses CD8+ T Cell Effector Function and Intestinal Inflammation
title_sort mir 29a b suppresses cd8 t cell effector function and intestinal inflammation
topic CD8+ T cell
differentiation
Ifng‐JAK‐STAT
miR‐29a/b
ulcerative colitis
url https://doi.org/10.1002/EXP.20240363
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