肠道菌群调控下17型辅助性T细胞及IL-17在骨关节炎发生发展中的作用研究进展

doi:10.3969/j.issn.1674-8115.2026.06.015

摘要/Abstract

摘要：

骨关节炎（osteoarthritis，OA）是目前全球范围内重要的致残原因，其病理认知正逐步从单纯“磨损性疾病”向“代谢与低度炎症性疾病”发生范式转变。肠道菌群作为宿主17型辅助性T细胞（T helper 17 cell，Th17细胞）的关键调控者，具有复杂的双向调节特性：一方面，菌群代谢产物（如短链脂肪酸、色氨酸代谢产物、次级胆汁酸）可通过表观遗传修饰［如抑制组蛋白脱乙酰酶（histone deacetylase，HDAC）］及激活特定受体［如G蛋白偶联受体43（G-protein-coupled receptor 43，GPR43）、芳香烃受体（aryl hydrocarbon receptor，AHR）、G蛋白偶联胆汁酸受体1（G protein-coupled bile acid receptor 1，GPBAR1，又称TGR5）］，维持Th17细胞/调节性T细胞（regulatory T cell，Treg细胞）平衡，发挥抗炎保护效应；另一方面，菌群结构组分（如脂多糖、细菌外囊泡）则通过模式识别受体激活致炎通路，进而诱导Th17细胞分化。进一步研究表明，肠道来源的Th17细胞及其效应因子白细胞介素-17（interleukin-17，IL-17）是连接肠道微生态失调与关节病变的核心纽带，Th17细胞及IL-17迁移至关节局部后充当炎症“放大器”，不仅能诱导滑膜成纤维细胞活化和炎症级联反应，还可直接驱动软骨细胞基质降解、衰老及铁死亡，并促进软骨下骨异常重塑，最终导致全关节结构破坏。该文旨在综述“肠道菌群-Th17细胞/IL-17免疫”轴在OA发生发展中的作用及相关分子机制。深入阐明该轴系的分子调控机制，有望为靶向肠道微生态治疗OA提供新的策略。

关键词: 骨关节炎, 肠道菌群, 白细胞介素-17, 17型辅助性T细胞

Abstract:

Osteoarthritis (OA) is a leading cause of disability worldwide, and the understanding of its pathogenesis is undergoing a paradigm shift from a simple "wear-and-tear" disease to a metabolic and low-grade inflammatory disorder. The gut microbiota, as a crucial regulator of host T helper 17 (Th17) cells, exhibits complex bidirectional modulatory characteristics. On one hand, microbial metabolites (such as short-chain fatty acids, tryptophan metabolites, and secondary bile acids) help maintain the balance between Th17 cells and regulatory T (Treg) cells, thereby exerting anti-inflammatory and protective effects. These effects are mediated through epigenetic modifications, such as inhibition of histone deacetylase (HDAC), and activation of specific receptors including G-protein-coupled receptor 43 (GPR43), aryl hydrocarbon receptor (AHR), and G-protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5). On the other hand, structural components of the microbiota (such as lipopolysaccharides and bacterial extracellular vesicles) activate pro-inflammatory pathways via pattern recognition receptors, thereby promoting Th17 cell differentiation. Further studies have shown that gut-derived Th17 cells and their effector cytokine cytokine interleukin-17 (IL-17) serve as a pivotal link connecting gut dysbiosis and joint pathology. After migrating to the joints, Th17 cells and IL-17 act as inflammatory "amplifiers". They not only induce synovial fibroblast activation and inflammatory cascades, but also directly drive cartilage matrix degradation, senescence, and ferroptosis, while promoting abnormal subchondral bone remodelling, ultimately leading to comprehensive destruction of the joint structure. This review aims to summarize the role of the "gut microbiota-Th17/IL-17 immune" axis in the pathogenesis and progression of OA, as well as the related molecular mechanisms. Elucidating the underlying molecular mechanisms of this axis holds promise for providing novel strategies for OA treatment targeting the gut microbiota.

Key words: osteoarthritis, gut microbiota, interleukin-17 (IL-17), T helper 17 (Th17) cell

中图分类号:

R684.3

龚继安, 韩稷钰, 万大千. 肠道菌群调控下17型辅助性T细胞及IL-17在骨关节炎发生发展中的作用研究进展[J]. 上海交通大学学报（医学版）, 2026, 46(6): 815-823.

Gong Jian, Han Jiyu, Wan Daqian. Research progress in role of T helper 17 cells and interleukin-17 in occurrence and development of osteoarthritis under regulation of gut microbiota[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026, 46(6): 815-823.

图/表 2

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Pathogenic process	Biological effect	Target cell/tissue	Key molecule/pathway/specific mechanism	Reference
Inflammatory amplification	Production of IL-1β, TNF, and IL-6	Chondrocytes	IL-1β, TNF, and IL-6	Kapoor et al, 2011^[37]
	IL-18 production and inflammation aggravation	Synovial fibroblasts	IL-18/MEK/ERK/miR-4492	Lee et al, 2024^[40]
	NET formation and fibroblast activation	Neutrophils, synovial fibroblasts	NETs	Khandpur et al, 2013^[41]
Cartilage matrix degradation	Pro-inflammatory and catabolic gene alteration	Chondrocytes	‒	Pemmari et al, 2021^[42]
	MMP-13 upregulation and cartilage/meniscus damage	Chondrocytes, meniscal cells	MMP-13	Wang et al, 2020^[43]
	MMP and IL-6 hyperproduction	Th17 cells, chondrocytes	MMP-1/3/9/13, IL-6	Platzer et al, 2025^[45]
	MDSC-driven Th17 differentiation and cartilage degradation	MDSCs, Th17 cells	MMPs	Guo et al, 2025^[46]
	NO/PGE2 production and catabolic shift	Chondrocytes	NO, PGE2	Denoble et al, 2011^[47]
	SASP induction and chronic inflammation	Chondrocytes	Senescence-associated secretory phenotype (SASP)	Faust et al, 2020^[48]
	GPX4 suppression and ferroptosis	Chondrocytes	IL-17/GPX4 axis, ferroptosis	Zhao et al, 2025^[49]
Subchondral bone remodeling	IL-17F/IL-23-associated bone marrow lesions	Subchondral bone	IL-17F, IL-23	Zhu et al, 2017^[51]
	RANKL/Beclin-1-driven osteoclastogenesis	Osteoblasts, osteoclasts	Beclin-1, RANKL	Chen et al, 2024^[50]
Synovitis and angiogenesis	ER stress-mediated synovial inflammation	Synovial fibroblasts	ER stress	Sun et al, 2025^[4]
	Autophagosome accumulation and mtSTAT3 suppression	Synovial fibroblasts	mtSTAT3	Lee et al, 2025^[52]
	VEGF-driven angiogenesis and synovial hyperplasia	Chondrocytes, synovial fibroblasts	VEGF	Mukherjee et al, 2024^[53]
	CD13-mediated T cell chemoattraction	Synovium, T cells	CD13	Morgan et al, 2015^[54]

Pathogenic process	Biological effect	Target cell/tissue	Key molecule/pathway/specific mechanism	Reference
Inflammatory amplification	Production of IL-1β, TNF, and IL-6	Chondrocytes	IL-1β, TNF, and IL-6	Kapoor et al, 2011^[37]
	IL-18 production and inflammation aggravation	Synovial fibroblasts	IL-18/MEK/ERK/miR-4492	Lee et al, 2024^[40]
	NET formation and fibroblast activation	Neutrophils, synovial fibroblasts	NETs	Khandpur et al, 2013^[41]
Cartilage matrix degradation	Pro-inflammatory and catabolic gene alteration	Chondrocytes	‒	Pemmari et al, 2021^[42]
	MMP-13 upregulation and cartilage/meniscus damage	Chondrocytes, meniscal cells	MMP-13	Wang et al, 2020^[43]
	MMP and IL-6 hyperproduction	Th17 cells, chondrocytes	MMP-1/3/9/13, IL-6	Platzer et al, 2025^[45]
	MDSC-driven Th17 differentiation and cartilage degradation	MDSCs, Th17 cells	MMPs	Guo et al, 2025^[46]
	NO/PGE2 production and catabolic shift	Chondrocytes	NO, PGE2	Denoble et al, 2011^[47]
	SASP induction and chronic inflammation	Chondrocytes	Senescence-associated secretory phenotype (SASP)	Faust et al, 2020^[48]
	GPX4 suppression and ferroptosis	Chondrocytes	IL-17/GPX4 axis, ferroptosis	Zhao et al, 2025^[49]
Subchondral bone remodeling	IL-17F/IL-23-associated bone marrow lesions	Subchondral bone	IL-17F, IL-23	Zhu et al, 2017^[51]
	RANKL/Beclin-1-driven osteoclastogenesis	Osteoblasts, osteoclasts	Beclin-1, RANKL	Chen et al, 2024^[50]
Synovitis and angiogenesis	ER stress-mediated synovial inflammation	Synovial fibroblasts	ER stress	Sun et al, 2025^[4]
	Autophagosome accumulation and mtSTAT3 suppression	Synovial fibroblasts	mtSTAT3	Lee et al, 2025^[52]
	VEGF-driven angiogenesis and synovial hyperplasia	Chondrocytes, synovial fibroblasts	VEGF	Mukherjee et al, 2024^[53]
	CD13-mediated T cell chemoattraction	Synovium, T cells	CD13	Morgan et al, 2015^[54]