Research progress on the role of dendritic cells in immune metabolism of rheumatoid arthritis_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

HAN Guangtao , SUN Shuo , WANG Qin ,  KANG Pengde

Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P. R. China;

Corresponding author：

KANG Pengde, Email: kangpengde69@126.com

Keywords：

Rheumatoid arthritis; dendritic cells; metabolic characteristics; immune metabolism

DOI：

10.7507/1002-1892.202408002

Video：

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Objective To review the role of dendritic cells (DC) in immune metabolism of rheumatoid arthritis (RA). Methods Literature on the role of DC in the immune metabolism of RA was extensively reviewed in recent years, and the metabolic characteristics of RA, the role of DC in RA, the correlation between the immune metabolism of DC and RA, and the treatment were summarized and analyzed. Results DC promotes the progression of RA under hypoxia, increased glycolysis, inhibition of oxidative phosphorylation, and decreased lipid metabolism. Moreover, many DCs (especially conventional DC and monocyte-derived DC) have different functions and phenotypic characteristics in RA, which are closely related to the occurrence and development of RA. Conclusion DC plays an important role in the immune metabolism of RA, and immunometabolism therapy based on DC can provide targeted therapy for the treatment of RA.

1.	Marzaioli V, Canavan M, Floudas A, et al. CD209/CD14+ dendritic cells characterization in rheumatoid and psoriatic arthritis patients: activation, synovial infiltration, and therapeutic targeting. Front Immunol, 2022, 12: 722349. doi: 10.3389/fimmu.2021.722349.
2.	Zhou S, Lu H, Xiong M. Identifying immune cell infiltration and effective diagnostic biomarkers in rheumatoid arthritis by bioinformatics analysis. Front Immunol, 2021, 12: 726747. doi: 10.3389/fimmu.2021.726747.
3.	李梦园, 钟兵, 常玲, 等. 类风湿性关节炎中树突状细胞亚群分析. 免疫学杂志, 2021, 37(4): 345-350.
4.	史向辉, 严婷婷, 沈洁, 等. RA患者外周血Breg、mDC和Th细胞水平与其病情程度及疾病活动程度的相关性. 浙江中西医结合杂志, 2021, 31(11): 1020-1023.
5.	张振, 孙晓彤, 邬秀娣, 等. IL-34对类风湿关节炎髓系树突状细胞表型的影响. 中国免疫学杂志, 2018, 34(4): 564-568.
6.	Jia XY, Chang Y, Sun XJ, et al. The role of prostaglandin E2 receptor signaling of dendritic cells in rheumatoid arthritis. Int Immunopharmacol, 2014, 23(1): 163-169.
7.	Qiao H, Mei J, Yuan K, et al. Immune-regulating strategy against rheumatoid arthritis by inducing tolerogenic dendritic cells with modified zinc peroxide nanoparticles. J Nanobiotechnology, 2022, 20(1): 323. doi: 10.1186/s12951-022-01536-0.
8.	Papadaki G, Goutakoli P, Tiniakou I, et al. IL-6 signaling attenuates TNF-α production by plasmacytoid dendritic cells in rheumatoid arthritis. J Immunol, 2022, 209(10): 1906-1917.
9.	Tian Y, Shi P, Zhou Y, et al. DiR-labeled tolerogenic dendritic cells for targeted imaging in collagen- induced arthritis rats. Int Immunopharmacol, 2021, 91: 107273. doi: 10.1016/j.intimp.2020.107273.
10.	Umbreen H, Zhang X, Tang KT, et al. Regulation of myeloid dendritic cells by synthetic and natural compounds for the treatment of rheumatoid arthritis. Int J Mol Sci, 2022, 24(1): 238. doi: 10.3390/ijms24010238.
11.	Yi O, Lin Y, Hu M, et al. Lactate metabolism in rheumatoid arthritis: Pathogenic mechanisms and therapeutic intervention with natural compounds. Phytomedicine, 2022, 100: 154048. doi: 10.1016/j.phymed.2022.154048.
12.	Martens PJ, Gysemans C, Verstuyf A, et al. Vitamin D’s effect on immune function. Nutrients, 2020, 12(5): 1248. doi: 10.3390/nu12051248.
13.	Wang J, Xue Y, Zhou L. Comparison of immune cells and diagnostic markers between spondyloarthritis and rheumatoid arthritis by bioinformatics analysis. J Transl Med, 2022, 20(1): 196. doi: 10.1186/s12967-022-03390-y.
14.	Moudgil KD, Venkatesha SH. The anti-inflammatory and immunomodulatory activities of natural products to control autoimmune inflammation. Int J Mol Sci, 2022, 24(1): 95. doi: 10.3390/ijms24010095.
15.	Canavan M, Marzaioli V, McGarry T, et al. Rheumatoid arthritis synovial microenvironment induces metabolic and functional adaptations in dendritic cells. Clin Exp Immunol, 2020, 202(2): 226-238.
16.	Coutant F. Shaping of monocyte-derived dendritic cell development and function by environmental factors in rheumatoid arthritis. Int J Mol Sci, 2021, 22(24): 13670. doi: 10.3390/ijms222413670.
17.	Thomas R. Dendritic cells and the promise of antigen-specific therapy in rheumatoid arthritis. Arthritis Res Ther, 2013, 15(1): 204. doi: 10.1186/ar4130.
18.	Fang Q, Zhou C, Nandakumar KS. Molecular and cellular pathways contributing to joint damage in rheumatoid arthritis. Mediators Inflamm, 2020, 2020: 3830212. doi: 10.1155/2020/3830212.
19.	Spiering R, Jansen MAA, Wood MJ, et al. Targeting of tolerogenic dendritic cells to heat-shock proteins in inflammatory arthritis. J Transl Med, 2019, 17(1): 375. doi: 10.1186/s12967-019-2128-4.
20.	Cooles FAH, Anderson AE, Skelton A, et al. Phenotypic and transcriptomic analysis of peripheral blood plasmacytoid and conventional dendritic cells in early drug naïve rheumatoid arthritis. Front Immunol, 2018, 9: 755. doi: 10.3389/fimmu.2018.00755.
21.	Lee ES, Sul JH, Shin JM, et al. Reactive oxygen species-responsive dendritic cell-derived exosomes for rheumatoid arthritis. Acta Biomater, 2021, 128: 462-473.
22.	Schittenhelm L, Robertson J, Pratt AG, et al. Dendritic cell integrin expression patterns regulate inflammation in the rheumatoid arthritis joint. Rheumatology (Oxford), 2021, 60(3): 1533-1542.
23.	Wang XY, Zhang JY. Treatment mechanism of tolerogenic dendritic cells on rheumatoid arthritis. J Biol Regul Homeost Agents, 2018, 32(5): 1239-1244.
24.	Feng X, Chen Y. Drug delivery targets and systems for targeted treatment of rheumatoid arthritis. J Drug Target, 2018, 26(10): 845-857.
25.	Geng Q, Xu J, Cao X, et al. PPARG-mediated autophagy activation alleviates inflammation in rheumatoid arthritis. J Autoimmun, 2024, 146: 103214. doi: 10.1016/j.jaut.2024.103214.
26.	Zhou Y, Leng X, Luo S, et al. Tolerogenic dendritic cells generated with tofacitinib ameliorate experimental autoimmune encephalomyelitis through modulation of Th17/Treg balance. J Immunol Res, 2016, 2016: 5021537. doi: 10.1155/2016/5021537.
27.	Abdallah MS, Alarfaj SJ, Saif DS, et al. The AMPK modulator metformin as adjunct to methotrexate in patients with rheumatoid arthritis: A proof-of-concept, randomized, double-blind, placebo-controlled trial. Int Immunopharmacol, 2021, 95: 107575. doi: 10.1016/j.intimp.2021.107575.
28.	Tan Y, Buch MH. ‘Difficult to treat’ rheumatoid arthritis: current position and considerations for next steps. RMD Open, 2022, 8(2): e002387. doi: 10.1136/rmdopen-2022-002387.
29.	Iwata M, Takada A, Sakamoto R, et al. The active form of vitamin D (calcitriol) promotes CXCR5 expression during follicular helper T cell differentiation. Int Immunol, 2024. doi: 10.1093/intimm/dxae045.
30.	Calabresi E, Petrelli F, Bonifacio AF, et al. One year in review 2018: pathogenesis of rheumatoid arthritis. Clin Exp Rheumatol, 2018, 36(2): 175-184.
31.	Gan PR, Wu H, Zhu YL, et al. Glycolysis, a driving force of rheumatoid arthritis. Int Immunopharmacol, 2024, 132: 111913. doi: 10.1016/j.intimp.2024.111913.
32.	Ah Kioon MD, Laurent P, Chaudhary V, et al. Modulation of plasmacytoid dendritic cells response in inflammation and autoimmunity. Immunol Rev, 2024, 323(1): 241-256.
33.	Garcia-Hernandez ML, Rangel-Moreno J, Garcia-Castaneda M, et al. Dendritic cell-specific transmembrane protein is required for synovitis and bone resorption in inflammatory arthritis. Front Immunol, 2022, 13: 1026574. doi: 10.3389/fimmu.2022.1026574.

1. Marzaioli V, Canavan M, Floudas A, et al. CD209/CD14+ dendritic cells characterization in rheumatoid and psoriatic arthritis patients: activation, synovial infiltration, and therapeutic targeting. Front Immunol, 2022, 12: 722349. doi: 10.3389/fimmu.2021.722349.
2. Zhou S, Lu H, Xiong M. Identifying immune cell infiltration and effective diagnostic biomarkers in rheumatoid arthritis by bioinformatics analysis. Front Immunol, 2021, 12: 726747. doi: 10.3389/fimmu.2021.726747.
3. 李梦园, 钟兵, 常玲, 等. 类风湿性关节炎中树突状细胞亚群分析. 免疫学杂志, 2021, 37(4): 345-350.
4. 史向辉, 严婷婷, 沈洁, 等. RA患者外周血Breg、mDC和Th细胞水平与其病情程度及疾病活动程度的相关性. 浙江中西医结合杂志, 2021, 31(11): 1020-1023.
5. 张振, 孙晓彤, 邬秀娣, 等. IL-34对类风湿关节炎髓系树突状细胞表型的影响. 中国免疫学杂志, 2018, 34(4): 564-568.
6. Jia XY, Chang Y, Sun XJ, et al. The role of prostaglandin E2 receptor signaling of dendritic cells in rheumatoid arthritis. Int Immunopharmacol, 2014, 23(1): 163-169.
7. Qiao H, Mei J, Yuan K, et al. Immune-regulating strategy against rheumatoid arthritis by inducing tolerogenic dendritic cells with modified zinc peroxide nanoparticles. J Nanobiotechnology, 2022, 20(1): 323. doi: 10.1186/s12951-022-01536-0.
8. Papadaki G, Goutakoli P, Tiniakou I, et al. IL-6 signaling attenuates TNF-α production by plasmacytoid dendritic cells in rheumatoid arthritis. J Immunol, 2022, 209(10): 1906-1917.
9. Tian Y, Shi P, Zhou Y, et al. DiR-labeled tolerogenic dendritic cells for targeted imaging in collagen- induced arthritis rats. Int Immunopharmacol, 2021, 91: 107273. doi: 10.1016/j.intimp.2020.107273.
10. Umbreen H, Zhang X, Tang KT, et al. Regulation of myeloid dendritic cells by synthetic and natural compounds for the treatment of rheumatoid arthritis. Int J Mol Sci, 2022, 24(1): 238. doi: 10.3390/ijms24010238.
11. Yi O, Lin Y, Hu M, et al. Lactate metabolism in rheumatoid arthritis: Pathogenic mechanisms and therapeutic intervention with natural compounds. Phytomedicine, 2022, 100: 154048. doi: 10.1016/j.phymed.2022.154048.
12. Martens PJ, Gysemans C, Verstuyf A, et al. Vitamin D’s effect on immune function. Nutrients, 2020, 12(5): 1248. doi: 10.3390/nu12051248.
13. Wang J, Xue Y, Zhou L. Comparison of immune cells and diagnostic markers between spondyloarthritis and rheumatoid arthritis by bioinformatics analysis. J Transl Med, 2022, 20(1): 196. doi: 10.1186/s12967-022-03390-y.
14. Moudgil KD, Venkatesha SH. The anti-inflammatory and immunomodulatory activities of natural products to control autoimmune inflammation. Int J Mol Sci, 2022, 24(1): 95. doi: 10.3390/ijms24010095.
15. Canavan M, Marzaioli V, McGarry T, et al. Rheumatoid arthritis synovial microenvironment induces metabolic and functional adaptations in dendritic cells. Clin Exp Immunol, 2020, 202(2): 226-238.
16. Coutant F. Shaping of monocyte-derived dendritic cell development and function by environmental factors in rheumatoid arthritis. Int J Mol Sci, 2021, 22(24): 13670. doi: 10.3390/ijms222413670.
17. Thomas R. Dendritic cells and the promise of antigen-specific therapy in rheumatoid arthritis. Arthritis Res Ther, 2013, 15(1): 204. doi: 10.1186/ar4130.
18. Fang Q, Zhou C, Nandakumar KS. Molecular and cellular pathways contributing to joint damage in rheumatoid arthritis. Mediators Inflamm, 2020, 2020: 3830212. doi: 10.1155/2020/3830212.
19. Spiering R, Jansen MAA, Wood MJ, et al. Targeting of tolerogenic dendritic cells to heat-shock proteins in inflammatory arthritis. J Transl Med, 2019, 17(1): 375. doi: 10.1186/s12967-019-2128-4.
20. Cooles FAH, Anderson AE, Skelton A, et al. Phenotypic and transcriptomic analysis of peripheral blood plasmacytoid and conventional dendritic cells in early drug naïve rheumatoid arthritis. Front Immunol, 2018, 9: 755. doi: 10.3389/fimmu.2018.00755.
21. Lee ES, Sul JH, Shin JM, et al. Reactive oxygen species-responsive dendritic cell-derived exosomes for rheumatoid arthritis. Acta Biomater, 2021, 128: 462-473.
22. Schittenhelm L, Robertson J, Pratt AG, et al. Dendritic cell integrin expression patterns regulate inflammation in the rheumatoid arthritis joint. Rheumatology (Oxford), 2021, 60(3): 1533-1542.
23. Wang XY, Zhang JY. Treatment mechanism of tolerogenic dendritic cells on rheumatoid arthritis. J Biol Regul Homeost Agents, 2018, 32(5): 1239-1244.
24. Feng X, Chen Y. Drug delivery targets and systems for targeted treatment of rheumatoid arthritis. J Drug Target, 2018, 26(10): 845-857.
25. Geng Q, Xu J, Cao X, et al. PPARG-mediated autophagy activation alleviates inflammation in rheumatoid arthritis. J Autoimmun, 2024, 146: 103214. doi: 10.1016/j.jaut.2024.103214.
26. Zhou Y, Leng X, Luo S, et al. Tolerogenic dendritic cells generated with tofacitinib ameliorate experimental autoimmune encephalomyelitis through modulation of Th17/Treg balance. J Immunol Res, 2016, 2016: 5021537. doi: 10.1155/2016/5021537.
27. Abdallah MS, Alarfaj SJ, Saif DS, et al. The AMPK modulator metformin as adjunct to methotrexate in patients with rheumatoid arthritis: A proof-of-concept, randomized, double-blind, placebo-controlled trial. Int Immunopharmacol, 2021, 95: 107575. doi: 10.1016/j.intimp.2021.107575.
28. Tan Y, Buch MH. ‘Difficult to treat’ rheumatoid arthritis: current position and considerations for next steps. RMD Open, 2022, 8(2): e002387. doi: 10.1136/rmdopen-2022-002387.
29. Iwata M, Takada A, Sakamoto R, et al. The active form of vitamin D (calcitriol) promotes CXCR5 expression during follicular helper T cell differentiation. Int Immunol, 2024. doi: 10.1093/intimm/dxae045.
30. Calabresi E, Petrelli F, Bonifacio AF, et al. One year in review 2018: pathogenesis of rheumatoid arthritis. Clin Exp Rheumatol, 2018, 36(2): 175-184.
31. Gan PR, Wu H, Zhu YL, et al. Glycolysis, a driving force of rheumatoid arthritis. Int Immunopharmacol, 2024, 132: 111913. doi: 10.1016/j.intimp.2024.111913.
32. Ah Kioon MD, Laurent P, Chaudhary V, et al. Modulation of plasmacytoid dendritic cells response in inflammation and autoimmunity. Immunol Rev, 2024, 323(1): 241-256.
33. Garcia-Hernandez ML, Rangel-Moreno J, Garcia-Castaneda M, et al. Dendritic cell-specific transmembrane protein is required for synovitis and bone resorption in inflammatory arthritis. Front Immunol, 2022, 13: 1026574. doi: 10.3389/fimmu.2022.1026574.

Chinese Journal of Reparative and Reconstructive Surgery

Latest ArticlesResearch progress on the role of dendritic cells in immune metabolism of rheumatoid arthritis

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