Research progress in role of T helper 17 cells and interleukin-17 in occurrence and development of osteoarthritis under regulation of gut microbiota

doi:10.3969/j.issn.1674-8115.2026.06.015

Abstract

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

CLC Number:

R684.3

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.

Figures/Tables 2

TrendMD

References 56

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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]