Study of the mechanism of helper T cells in the pathogenesis of osteoarthritis_West China Medical Journal

Authors：

XUE Zhirui ¹ , SONG Hanbing ² , LIU Jiaxing ² ,  JIANG Yichang ²

1. Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P. R. China;
2. Department of Orthopedics and Traumatology, First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P. R. China;

Corresponding?author：

JIANG Yichang, Email: jiangyichang2008@126.com

Keywords：

Osteoarthritis; helper T cells; helper T 17 cells; regulatory T cells; immunotherapy; inflammatory microenvironment

DOI：

10.7507/1002-0179.202506021

Video：

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Osteoarthritis (OA) is a chronic degenerative disease characterized by cartilage degeneration, synovial inflammation, and abnormal bone remodeling. Emerging evidence indicates that helper T (Th) cells play a pivotal role in OA pathogenesis. In the OA joint microenvironment, a marked imbalance among Th cell subsets is observed, manifested as overactivation of Th1 and Th17 cells alongside impaired function of Th2 and regulatory T cells. This imbalance leads to elevated levels of pro-inflammatory cytokines, such as interleukin (IL)-17, interferon-gamma, and tumor necrosis factor-alpha, whereas anti-inflammatory cytokines, including IL-4 and IL-10, are relatively deficient, resulting in chondrocyte apoptosis, extracellular matrix degradation, and synovial inflammation. This article systematically summarizes the molecular mechanisms of different Th cell subsets in OA development and elucidate their synergistic interactions with macrophages, providing a theoretical basis for Th cell-targeted immunomodulatory strategies in OA therapy.

Citation： XUE Zhirui, SONG Hanbing, LIU Jiaxing, JIANG Yichang. Study of the mechanism of helper T cells in the pathogenesis of osteoarthritis. West China Medical Journal, 2026, 41(4): 675-679. doi: 10.7507/1002-0179.202506021 Copy

1.	Allen KD, Thoma LM, Golightly YM. Epidemiology of osteoarthritis. Osteoarthritis Cartilage, 2022, 30(2): 184-195.
2.	Coaccioli S, Sarzi-Puttini P, Zis P, et al. Osteoarthritis: new insight on its pathophysiology. J Clin Med, 2022, 11(20): 6013.
3.	Saravia J, Chapman NM, Chi H. Helper T cell differentiation. Cell Mol Immunol, 2019, 16(7): 634-643.
4.	Sengprasert P, Kamenkit O, Tanavalee A, et al. The immunological facets of chondrocytes in osteoarthritis: a narrative review.J Rheumatol, 2023: jrheum. 2023-0816.
5.	Adu-Berchie K, Obuseh FO, Mooney DJ. T cell development and function. Rejuvenation Re, 2023, 26(4): 126-138.
6.	Li YS, Luo W, Zhu SA, et al. T cells in osteoarthritis: alterations and beyond. Front Immunol, 2017, 8: 356.
7.	Wijesinghe SN, Ditchfield C, Flynn S, et al. Immunomodulation and fibroblast dynamics driving nociceptive joint pain within inflammatory synovium: unravelling mechanisms for therapeutic advancements in osteoarthritis. Osteoarthritis Cartilage, 2024, 32(11): 1358-1370.
8.	Da Z, Guo R, Sun J, et al. Identification of osteoarthritis-characteristic genes and immunological micro-environment features through bioinformatics and machine learning-based approaches. BMC Med Genomics, 2023, 16(1): 236.
9.	Wheeler TA, Antoinette AY, Bhatia E, et al. Mechanical loading of joint modulates T cells in lymph nodes to regulate osteoarthritis. Osteoarthritis Cartilage, 2024, 32(3): 287-298.
10.	Shen PC, Wu CL, Jou IM, et al. T helper cells promote disease progression of osteoarthritis by inducing macrophage inflammatory protein-1γ. Osteoarthritis Cartilage, 2011, 19(6): 728-736.
11.	Kokubo K, Onodera A, Kiuchi M, et al. Conventional and pathogenic Th2 cells in inflammation, tissue repair, and fibrosis. Front Immunol, 2022, 13: 945063.
12.	Pemmari A, Lepp?nen T, H?m?l?inen M, et al. Chondrocytes from osteoarthritis patients adopt distinct phenotypes in response to central T_H1/T_H2/T_H17 cytokines. Int J Mol Sci, 2021, 22(17): 9463.
13.	Ko CY, Lin YY, Achudhan D, et al. Omentin-1 ameliorates the progress of osteoarthritis by promoting IL-4-dependent anti-inflammatory responses and M2 macrophage polarization. IntJ Biol Sci, 2023, 19(16): 5275-5289.
14.	Wang H, Fang K, Yan W, et al. T-cell immune imbalance in rheumatoid arthritis is associated with alterations in NK cells and NK-like T cells expressing CD38. J Innate Immun, 2022, 14(2): 148-166.
15.	Wang Q, Wang Y, Liu Q, et al. MALT1 regulates Th2 and Th17 differentiation via NF-κB and JNK pathways, as well as correlates with disease activity and treatment outcome in rheumatoid arthritis. Front Immunol, 2022, 13: 913830.
16.	Korsten SGPJ, Hartog M, Berends AJ, et al. A sustained-release butyrate tablet suppresses Ex Vivo T helper cell activation of osteoarthritis patients in a double-blind placebo-controlled randomized trial. Nutrients, 2024, 16(19): 3384.
17.	Hu K, Song M, Song T, et al. Osteoimmunology in osteoarthritis: unraveling the interplay of immunity, inflammation, and joint degeneration. J Inflamm Res, 2025: 4121-4142.
18.	Hao G, Han S, Xiao Z, et al. Synovial mast cells and osteoarthritis: current understandings and future perspectives. Heliyon, 2024, 10(24): e41003.
19.	Zhu L, Hua F, Ding W, et al. The correlation between the Th17/Treg cell balance and bone health. Immun Ageing, 2020, 17: 30.
20.	Schnell A, Littman DR, Kuchroo VK. T_H17 cell heterogeneity and its role in tissue inflammation. Nat Immunol, 2023, 24(1): 19-29.
21.	Na HS, Park JS, Cho KH, et al. Interleukin-1-interleukin-17 signaling axis induces cartilage destruction and promotes experimental osteoarthritis. Front Immunol, 2020, 11: 730.
22.	Yan Y, Li K, Jiang J, et al. Perinatal tissue-derived exosomes ameliorate colitis in mice by regulating the Foxp3+ Treg cells and gut microbiota. Stem Cell Res Ther, 2023, 14(1): 43.
23.	Nees TA, Zhang JA, Platzer H, et al. Infiltration profile of regulatory T cells in osteoarthritis-related pain and disability. Biomedicines, 2022, 10(9): 2111.
24.	Lopes EBP, Filiberti A, Husain SA, et al. Immune contributions to osteoarthritis. Curr Osteoporos Rep, 2017, 15(6): 593-600.
25.	Binvignat M, Dubois J, Tchitchek N, et al. Immunological profiling of pain in knee osteoarthritis: treg cells as potential new key players in symptomatic knee osteoarthritis. Osteoarthr Cartil, 2024, 32: S54-S55.
26.	Wang L, Wang Y, Liu C, et al. Treg-targeted efficient-inducible platform for collagen-induced arthritis treatment. Mater Today Bio, 2023, 19: 100557.
27.	Khokhar M, Purohit P. The emerging role of T helper 9 (Th9) cells in immunopathophysiology: a comprehensive review of their effects and responsiveness in various disease states. Int Rev Immunol, 2024, 43(6): 341-360.
28.	Tu J, Chen W, Huang W, et al. Positive feedback loop PU. 1-IL9 in Th9 promotes rheumatoid arthritis development. Ann Rheum Dis, 2024, 83(12): 1707-1721.
29.	Akiyama M, Alshehri W, Yoshimoto K, et al. T follicular helper cells and T peripheral helper cells in rheumatic and musculoskeletal diseases. Ann Rheum Dis, 2023, 82(11): 1371-1381.
30.	Jiang Q, Yang G, Xiao F, et al. Role of Th22 cells in the pathogenesis of autoimmune diseases. Front Immunol, 2021, 12: 688066.
31.	Miyazaki Y, Nakayamada S, Kubo S, et al. Th22 cells promote osteoclast differentiation via production of IL-22 in rheumatoid arthritis. Front Immunol, 2018, 9: 2901.
32.	Yadav S, Dwivedi A, Tripathi A. Biology of macrophage fate decision: implication in inflammatory disorders. Cell Biol Int, 2022, 46(10): 1539-1556.
33.	Murayama M, Chow SK, Lee ML, et al. The interactions of macrophages, lymphocytes, and mesenchymal stem cells during bone regeneration. Bone Joint Res, 2024, 13(9): 462-473.
34.	Cutolo M, Campitiello R, Gotelli E, et al. The role of M1/M2 macrophage polarization in rheumatoid arthritis synovitis. Front Immuno, 2022, 13: 867260.
35.	Fang C, Zhong R, Lu S, et al. TREM2 promotes macrophage polarization from M1 to M2 and suppresses osteoarthritis through the NF-κB/CXCL3 axis. Int J Biol Sci, 2024, 20(6): 1992-2007.
36.	Wang L, He C. Nrf2-mediated anti-inflammatory polarization of macrophages as therapeutic targets for osteoarthritis. Front Immunol, 2022, 13: 967193.
37.	Tu J, Huang W, Zhang W, et al. A tale of two immune cells in rheumatoid arthritis: the crosstalk between macrophages and T cells in the synovium. Front Immunol, 2021, 12: 655477.
38.	Chang JW, Tang CH. The role of macrophage polarization in rheumatoid arthritis and osteoarthritis: pathogenesis and therapeutic strategies. Int Immunopharmacol, 2024, 142 (Pt A): 113056.
39.	Okeke EB, Uzonna JE. The pivotal role of regulatory T cells in the regulation of innate immune cells. Front Immunol, 2019, 10: 680.

1. Allen KD, Thoma LM, Golightly YM. Epidemiology of osteoarthritis. Osteoarthritis Cartilage, 2022, 30(2): 184-195.
2. Coaccioli S, Sarzi-Puttini P, Zis P, et al. Osteoarthritis: new insight on its pathophysiology. J Clin Med, 2022, 11(20): 6013.
3. Saravia J, Chapman NM, Chi H. Helper T cell differentiation. Cell Mol Immunol, 2019, 16(7): 634-643.
4. Sengprasert P, Kamenkit O, Tanavalee A, et al. The immunological facets of chondrocytes in osteoarthritis: a narrative review.J Rheumatol, 2023: jrheum. 2023-0816.
5. Adu-Berchie K, Obuseh FO, Mooney DJ. T cell development and function. Rejuvenation Re, 2023, 26(4): 126-138.
6. Li YS, Luo W, Zhu SA, et al. T cells in osteoarthritis: alterations and beyond. Front Immunol, 2017, 8: 356.
7. Wijesinghe SN, Ditchfield C, Flynn S, et al. Immunomodulation and fibroblast dynamics driving nociceptive joint pain within inflammatory synovium: unravelling mechanisms for therapeutic advancements in osteoarthritis. Osteoarthritis Cartilage, 2024, 32(11): 1358-1370.
8. Da Z, Guo R, Sun J, et al. Identification of osteoarthritis-characteristic genes and immunological micro-environment features through bioinformatics and machine learning-based approaches. BMC Med Genomics, 2023, 16(1): 236.
9. Wheeler TA, Antoinette AY, Bhatia E, et al. Mechanical loading of joint modulates T cells in lymph nodes to regulate osteoarthritis. Osteoarthritis Cartilage, 2024, 32(3): 287-298.
10. Shen PC, Wu CL, Jou IM, et al. T helper cells promote disease progression of osteoarthritis by inducing macrophage inflammatory protein-1γ. Osteoarthritis Cartilage, 2011, 19(6): 728-736.
11. Kokubo K, Onodera A, Kiuchi M, et al. Conventional and pathogenic Th2 cells in inflammation, tissue repair, and fibrosis. Front Immunol, 2022, 13: 945063.
12. Pemmari A, Lepp?nen T, H?m?l?inen M, et al. Chondrocytes from osteoarthritis patients adopt distinct phenotypes in response to central T_H1/T_H2/T_H17 cytokines. Int J Mol Sci, 2021, 22(17): 9463.
13. Ko CY, Lin YY, Achudhan D, et al. Omentin-1 ameliorates the progress of osteoarthritis by promoting IL-4-dependent anti-inflammatory responses and M2 macrophage polarization. IntJ Biol Sci, 2023, 19(16): 5275-5289.
14. Wang H, Fang K, Yan W, et al. T-cell immune imbalance in rheumatoid arthritis is associated with alterations in NK cells and NK-like T cells expressing CD38. J Innate Immun, 2022, 14(2): 148-166.
15. Wang Q, Wang Y, Liu Q, et al. MALT1 regulates Th2 and Th17 differentiation via NF-κB and JNK pathways, as well as correlates with disease activity and treatment outcome in rheumatoid arthritis. Front Immunol, 2022, 13: 913830.
16. Korsten SGPJ, Hartog M, Berends AJ, et al. A sustained-release butyrate tablet suppresses Ex Vivo T helper cell activation of osteoarthritis patients in a double-blind placebo-controlled randomized trial. Nutrients, 2024, 16(19): 3384.
17. Hu K, Song M, Song T, et al. Osteoimmunology in osteoarthritis: unraveling the interplay of immunity, inflammation, and joint degeneration. J Inflamm Res, 2025: 4121-4142.
18. Hao G, Han S, Xiao Z, et al. Synovial mast cells and osteoarthritis: current understandings and future perspectives. Heliyon, 2024, 10(24): e41003.
19. Zhu L, Hua F, Ding W, et al. The correlation between the Th17/Treg cell balance and bone health. Immun Ageing, 2020, 17: 30.
20. Schnell A, Littman DR, Kuchroo VK. T_H17 cell heterogeneity and its role in tissue inflammation. Nat Immunol, 2023, 24(1): 19-29.
21. Na HS, Park JS, Cho KH, et al. Interleukin-1-interleukin-17 signaling axis induces cartilage destruction and promotes experimental osteoarthritis. Front Immunol, 2020, 11: 730.
22. Yan Y, Li K, Jiang J, et al. Perinatal tissue-derived exosomes ameliorate colitis in mice by regulating the Foxp3+ Treg cells and gut microbiota. Stem Cell Res Ther, 2023, 14(1): 43.
23. Nees TA, Zhang JA, Platzer H, et al. Infiltration profile of regulatory T cells in osteoarthritis-related pain and disability. Biomedicines, 2022, 10(9): 2111.
24. Lopes EBP, Filiberti A, Husain SA, et al. Immune contributions to osteoarthritis. Curr Osteoporos Rep, 2017, 15(6): 593-600.
25. Binvignat M, Dubois J, Tchitchek N, et al. Immunological profiling of pain in knee osteoarthritis: treg cells as potential new key players in symptomatic knee osteoarthritis. Osteoarthr Cartil, 2024, 32: S54-S55.
26. Wang L, Wang Y, Liu C, et al. Treg-targeted efficient-inducible platform for collagen-induced arthritis treatment. Mater Today Bio, 2023, 19: 100557.
27. Khokhar M, Purohit P. The emerging role of T helper 9 (Th9) cells in immunopathophysiology: a comprehensive review of their effects and responsiveness in various disease states. Int Rev Immunol, 2024, 43(6): 341-360.
28. Tu J, Chen W, Huang W, et al. Positive feedback loop PU. 1-IL9 in Th9 promotes rheumatoid arthritis development. Ann Rheum Dis, 2024, 83(12): 1707-1721.
29. Akiyama M, Alshehri W, Yoshimoto K, et al. T follicular helper cells and T peripheral helper cells in rheumatic and musculoskeletal diseases. Ann Rheum Dis, 2023, 82(11): 1371-1381.
30. Jiang Q, Yang G, Xiao F, et al. Role of Th22 cells in the pathogenesis of autoimmune diseases. Front Immunol, 2021, 12: 688066.
31. Miyazaki Y, Nakayamada S, Kubo S, et al. Th22 cells promote osteoclast differentiation via production of IL-22 in rheumatoid arthritis. Front Immunol, 2018, 9: 2901.
32. Yadav S, Dwivedi A, Tripathi A. Biology of macrophage fate decision: implication in inflammatory disorders. Cell Biol Int, 2022, 46(10): 1539-1556.
33. Murayama M, Chow SK, Lee ML, et al. The interactions of macrophages, lymphocytes, and mesenchymal stem cells during bone regeneration. Bone Joint Res, 2024, 13(9): 462-473.
34. Cutolo M, Campitiello R, Gotelli E, et al. The role of M1/M2 macrophage polarization in rheumatoid arthritis synovitis. Front Immuno, 2022, 13: 867260.
35. Fang C, Zhong R, Lu S, et al. TREM2 promotes macrophage polarization from M1 to M2 and suppresses osteoarthritis through the NF-κB/CXCL3 axis. Int J Biol Sci, 2024, 20(6): 1992-2007.
36. Wang L, He C. Nrf2-mediated anti-inflammatory polarization of macrophages as therapeutic targets for osteoarthritis. Front Immunol, 2022, 13: 967193.
37. Tu J, Huang W, Zhang W, et al. A tale of two immune cells in rheumatoid arthritis: the crosstalk between macrophages and T cells in the synovium. Front Immunol, 2021, 12: 655477.
38. Chang JW, Tang CH. The role of macrophage polarization in rheumatoid arthritis and osteoarthritis: pathogenesis and therapeutic strategies. Int Immunopharmacol, 2024, 142 (Pt A): 113056.
39. Okeke EB, Uzonna JE. The pivotal role of regulatory T cells in the regulation of innate immune cells. Front Immunol, 2019, 10: 680.

West China Medical Journal

Study of the mechanism of helper T cells in the pathogenesis of osteoarthritis

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