粪产碱杆菌通过促进E3泛素连接酶Trim21介导的Fbxw7蛋白降解诱导肠道Th17细胞应答，这一成果由浙江大学医学院蔡志坚研究团队经过不懈努力而取得。相关论文于2025年4月10日发表在《免疫学》杂志上。

小组报道了普遍存在的粪产碱杆菌的定植足以诱导肠道Th17细胞。粪产碱杆菌蛋白被CD4⁺ T细胞以依赖小GT酶 CDC42的方式内噬，抑制E2泛素结合酶Ube2w与E3泛素连接酶Trim21的相互作用，从而减少Trim21的自泛素化和降解，从而增加Trim21诱导的E3泛素连接酶Fbxw7降解和JunB积累，进而促进Ahr和Rorc转录，增强肠道Th17细胞分化。

此外，粪产碱杆菌外膜囊泡也以Trim21-Fbxw7轴依赖的方式诱导肠道Th17细胞。总之，这些结果揭示了Trim21-Fbxw7轴在大多数人肠道Th17细胞富集中的重要作用。

据悉，分节丝状细菌对肠道Th17细胞的诱导至关重要，但它们在成人肠道中的定植存在争议。因此，在不同年龄的人体内是否存在介导Th17细胞生成的肠道微生物群（gut microbiota, GMs）是未知的。

附：英文原文

Title: A. faecalis induces intestinal T helper 17 cells by promoting E3 ubiquitin ligase Trim21-mediated E3 ubiquitin ligase Fbxw7 degradation

Author: Yingying Shen, Zeyu Ma, Hanliang Wang, Yinghu Chen, Yue Fang, Lionel Apetoh, Gensheng Zhang, Fenglian He, Shaofang Xie, Jufeng Guo, Shuaikang Cao, Hai Li, Qingqing Wang, Jianli Wang, Junjie Xu, Zhijian Cai

Issue&Volume: 2025-04-10

Abstract: Segmented filamentous bacteria are essential for intestinal T helper 17 (Th17) cell induction, but their colonization in the adult intestine is controversial. Therefore, whether there are gut microbiota (GMs) that mediate Th17 cell generation in humans of different ages is elusive. Here, we reported that colonization of ubiquitous Alcaligenes faecalis was sufficient to induce intestinal Th17 cells. Alcaligenes faecalis proteins were endocytosed by CD4+ T cells in a manner dependent on the small GTPase CDC42, inhibiting the interaction between E2 ubiquitin-conjugating enzyme Ube2w and E3 ubiquitin ligase Trim21, thereby reducing Trim21 self-ubiquitination and degradation, which increased Trim21-induced E3 ubiquitin ligase Fbxw7 degradation and JunB accumulation, subsequently promoting Ahr and Rorc transcription, thus enhancing intestinal Th17 cell differentiation. Furthermore, outer membrane vesicles from Alcaligenes faecalis also induced intestinal Th17 cells in a Trim21-Fbxw7-axis-dependent manner. Altogether, these results reveal a vital role for the Trim21-Fbxw7 axis in intestinal Th17 cell enrichments among most humans.

DOI: 10.1016/j.immuni.2025.03.008

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00128-1