炎症性肠病模型小鼠肠道上皮间γδ T细胞的促炎功能

doi:10.16352/j.issn.1001-6325.2026.07.0913

基础医学与临床 ›› 2026, Vol. 46 ›› Issue (7): 913-924.doi: 10.16352/j.issn.1001-6325.2026.07.0913

炎症性肠病模型小鼠肠道上皮间γδ T细胞的促炎功能

许依^1*, 张斯雅², 张建民^1,3, 何维¹, 陈慧^1*

1.中国医学科学院基础医学研究所北京协和医学院基础医学院免疫学系重大疾病共性机制研究全国重点实验室,北京 100005;
2.北京佳德和细胞治疗技术有限公司,北京 100176;
3.常州西太湖细胞治疗前沿技术研究院,江苏常州 213000

收稿日期:2026-04-24 修回日期:2026-05-19 出版日期:2026-07-05 发布日期:2026-06-23
通讯作者: ^*xuyi@ibms.pumc.edu.cn; chenhui_1980@126.com
基金资助:
国家自然科学基金(32300745,32270915);中国医学科学院医学与健康科技创新工程(2025-I2M-KJ-012, 2021 I2M-1-053);常州西太湖细胞治疗前沿技术发展基金会项目(2024-P-010)

Pro-inflammatory functions of intestinal intraepithelial γδ T cells in mouse models of inflammatory bowel disease

XU Yi^1*, ZHANG Siya², ZHANG Jianmin^1,3, HE Wei¹, CHEN Hui^1*

1. State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005;
2. Beijing Jiadehe Cell Therapy Technology Co., Ltd, Beijing 100176;
3. Changzhou Xitaihu Institute for Frontier Technology of Cell Therapy, Changzhou 213000, China

Received:2026-04-24 Revised:2026-05-19 Online:2026-07-05 Published:2026-06-23
Contact: ^*xuyi@ibms.pumc.edu.cn; chenhui_1980@126.com

摘要/Abstract

摘要： 目的探究葡聚糖硫酸钠(DSS)诱导炎症性肠病(IBD)小鼠肠上皮间淋巴细胞(IELs)中γδ T细胞的促炎功能及机制。方法用γδ T细胞敲除(KO)和野生型(WT)小鼠,DSS诱导IBD,行疾病活动指数(DAI)和苏木精-伊红(HE)染色法评价组织损伤;用流式细胞测量术检测脾脏、淋巴结及IEL中γδ T细胞及其亚群比例、细胞因子分泌和分化簇(CD)27表达;进行全转录组测序(bulk RNA-seq)和γδ T细胞受体(TCR γδ)免疫组库测序分析。结果 DSS诱导后,γδ T细胞KO鼠较WT对照鼠,DAI降低(P＜0.05),肠黏膜组织破坏较轻;γδ T细胞在IEL中比例显著高于脾脏和淋巴结,DSS处理后,其比例进一步升高(P＜0.05),但其亚型Vγ1和Vγ4比例、γ干扰素(IFN-γ) 和白细胞介素17(IL-17)分泌水平及CD27表达差异无统计学意义;Bulk RNA-seq结果显示,γδ T细胞抗菌与抑炎基因下调(P＜0.05);TCR γδ免疫组库互补决定区(CDR)3多样性显著降低(P＜0.05)。结论 DSS诱导小鼠IBD模型中,IEL中γδ T细胞并非通过分泌促炎细胞因子驱动病程,而呈现CDR3多样性缩减、抗感染与免疫调节功能缺陷,促进组织炎性反应损伤。本研究可为IBD治疗提供新型干预思路。

关键词: 炎症性肠病(IBD), γδ T细胞, 肠上皮间淋巴细胞(IEL), 全转录组测序, 免疫组库

Abstract: Objective To investigate the pro-inflammatory function and mechanisms of γδ T cells derived from intestinal intraepithelial lymphocytes (IELs) in a mouse model of inflammatory bowel disease (IBD) induced by dextran sulfate sodium (DSS). Methods Mouse model of IBD was established by DSS administration in both γδ T cell knockout (KO) mice and in wild-type (WT) mice. Intestinal tissue damage was evaluated by the disease activity index (DAI) and hematoxylin-eosin (HE) staining microscopy. Flow cytometry was employed to analyze the proportion, subset composition, cytokine secretion, and surface cluster of differentiation (CD27) expression of γδ T cells isolated from the spleen(SPL), peripheral lymph nodes(LNs) and IEL.Bulk RNA sequencing(bulk RNA-seq) was performed to examine transcriptomic changes while and immune repertoire sequencing was used to evaluate the character of TCRγδ repertoire. Results Compared to WT controls, γδ T cell KO mice exhibited lower DAI scores(P＜0.05) and milder tissue damage following DSS administration. The proportion of γδ T cells in the IEL was higher than that in the spleen or peripheral lymph nodes but significantly increased after DSS treatment(P＜0.05). The relative proportions of Vγ1 and Vγ4 subsets,IFN-γ and IL-17 secretion, and surface CD27 expression did show any significant difference between untreated and DSS-treated groups. However, bulk RNA-seq analysis revealed a down regulation of anti-bacterial molecule genes and anti-inflammatory genes in DSS-treated mice(P＜0.05).Immune repertoire analysis showed that complementarity determining region(CDR)3 diversity in γδ T cells from DSS-induced mice was reduced significantly(P＜0.05). Conclusions IEL-derived γδ T cells promote intestinal inflammation in DSS-induced colitis via mechanisms that appear independent of pro-inflammatory cytokine secretion. These cells exhibit reduced inflammation-associated CDR3 diversity, impaired anti-microbial pathway activity, and disrupted immunoregulatory signaling. The results of this research may support the development of novel therapeutic strategies for IBD.

Key words: inflammatory bowel disease(IBD), γδ T cell, intestinal intraepithelial lymphocyte(IEL), bulk transcriptomic sequence, immune repertoire

中图分类号:

R392.12

许依, 张斯雅, 张建民, 何维, 陈慧. 炎症性肠病模型小鼠肠道上皮间γδ T细胞的促炎功能[J]. 基础医学与临床, 2026, 46(7): 913-924.

XU Yi, ZHANG Siya, ZHANG Jianmin, HE Wei, CHEN Hui. Pro-inflammatory functions of intestinal intraepithelial γδ T cells in mouse models of inflammatory bowel disease[J]. Basic & Clinical Medicine, 2026, 46(7): 913-924.

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炎症性肠病模型小鼠肠道上皮间γδ T细胞的促炎功能

Pro-inflammatory functions of intestinal intraepithelial γδ T cells in mouse models of inflammatory bowel disease

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