IMMUNE NETWORK

  • 제24권4호
  • /
  • Pages.32.1-32.13
  • /
  • 2024
  • /
  • 1598-2629(pISSN)
  • /
  • 2092-6685(eISSN)
대한면역학회 (The Korean Association of Immunobiologists)
권호 표지
DOI QR코드

DOI QR Code

Low-Dose Radiotherapy Attenuates Experimental Autoimmune Arthritis by Inducing Apoptosis of Lymphocytes and Fibroblast-Like Synoviocytes

  • Bo-Gyu Kim (Division of Rheumatology, Department of Internal Medicine, Gyeongsang National University Hospital) ;
  • Hoon Sik Choi (Department of Radiation Oncology, Gyeongsang National University Changwon Hospital) ;
  • Yong-ho Choe (Division of Rheumatology, Department of Internal Medicine, Gyeongsang National University Hospital) ;
  • Hyun Min Jeon (Division of Rheumatology, Department of Internal Medicine, Gyeongsang National University Hospital) ;
  • Ji Yeon Heo (Division of Rheumatology, Department of Internal Medicine, Gyeongsang National University Hospital) ;
  • Yun-Hong Cheon (Division of Rheumatology, Department of Internal Medicine, Gyeongsang National University Hospital) ;
  • Ki Mun Kang (Department of Radiation Oncology, Gyeongsang National University Changwon Hospital) ;
  • Sang-Il Lee (Division of Rheumatology, Department of Internal Medicine, Gyeongsang National University Hospital) ;
  • Bae Kwon Jeong (Department of Radiation Oncology and Institute of Health Science, College of Medicine, Gyeongsang National University) ;
  • Mingyo Kim (Division of Rheumatology, Department of Internal Medicine, Gyeongsang National University Hospital)
  • 투고 : 2023.12.23
  • 심사 : 2024.07.31
  • 발행 : 2024.08.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Low-dose radiotherapy (LDRT) has been explored as a treatment option for various inflammatory diseases; however, its application in the context of rheumatoid arthritis (RA) is lacking. This study aimed to elucidate the mechanism underlying LDRT-based treatment for RA and standardize it. LDRT reduced the total numbers of immune cells, but increased the apoptotic CD4+ T and B220+ B cells, in the draining lymph nodes of collagen induced arthritis and K/BxN models. In addition, it significantly reduced the severity of various pathological manifestations, including bone destruction, cartilage erosion, and swelling of hind limb ankle. Post-LDRT, the proportion of apoptotic CD4+ T and CD19+ B cells increased significantly in the PBMCs derived from human patients with RA. LDRT showed a similar effect in fibroblast-like synoviocytes as well. In conclusion, we report that LDRT induces apoptosis in immune cells and fibro-blast-like synoviocytes, contributing to attenuation of arthritis.

키워드

과제정보

This study was supported by grants from the Basic Science Research Program through the National Research Foundation of Korea (RS-2023-00219399), and biomedical research institute fund at Gyeongsang National University Hospital (GNUHBRIF-2021-0002).

참고문헌

  1. Scherer HU, Haupl T, Burmester GR. The etiology of rheumatoid arthritis. J Autoimmun 2020;110:102400.
  2. Wu J, Feng Z, Chen L, Li Y, Bian H, Geng J, Zheng ZH, Fu X, Pei Z, Qin Y, et al. TNF antagonist sensitizes synovial fibroblasts to ferroptotic cell death in collagen-induced arthritis mouse models. Nat Commun 2022;13:676.
  3. Baker KF, Isaacs JD, Thompson B. "Living a normal life": a qualitative study of patients' views of medication withdrawal in rheumatoid arthritis. BMC Rheumatol 2019;3:2.
  4. Zhao S, Mysler E, Moots RJ. Etanercept for the treatment of rheumatoid arthritis. Immunotherapy 2018;10:433-445. https://doi.org/10.2217/imt-2017-0155
  5. Escalante A, Beardmore TD. Risk factors for early wound complications after orthopedic surgery for rheumatoid arthritis. J Rheumatol 1995;22:1844-1851.
  6. Kawakami K, Ikari K, Kawamura K, Tsukahara S, Iwamoto T, Yano K, Sakuma Y, Tokita A, Momohara S. Complications and features after joint surgery in rheumatoid arthritis patients treated with tumour necrosis factor-alpha blockers: perioperative interruption of tumour necrosis factor-alpha blockers decreases complications? Rheumatology (Oxford) 2010;49:341-347. https://doi.org/10.1093/rheumatology/kep376
  7. Rithidech KN. Health benefits of exposure to low-dose radiation. Health Phys 2016;110:293-295. https://doi.org/10.1097/HP.0000000000000430
  8. Torres Royo L, Antelo Redondo G, Arquez Pianetta M, Arenas Prat M. Low-dose radiation therapy for benign pathologies. Rep Pract Oncol Radiother 2020;25:250-254. https://doi.org/10.1016/j.rpor.2020.02.004
  9. Budras KD, Hartung K, Munzer BM. Light and electron microscopy studies of the effect of roentgen irradiation on the synovial membrane of the inflamed knee joint. Berl Munch Tierarztl Wochenschr 1986;99:148-152.
  10. Fischer U, Kamprad F, Koch F, Ludewig E, Melzer R, Hildebrandt G. The effects of low-dose Co-60 irradiation on the course of aseptic arthritis in a rabbit knee joint. Strahlenther Onkol 1998;174:633-639. https://doi.org/10.1007/BF03038512
  11. Calabrese EJ, Calabrese V. Reduction of arthritic symptoms by low dose radiation therapy (LD-RT) is associated with an anti-inflammatory phenotype. Int J Radiat Biol 2013;89:278-286. https://doi.org/10.3109/09553002.2013.752594
  12. Kim BH, Bae HC, Wang SY, Jang BS, Chang JH, Chie EK, Yi HS, Kwon J, Han HS, Kim HJ. Low-dose irradiation could mitigate osteoarthritis progression via anti-inflammatory action that modulates mitochondrial function. Radiother Oncol 2022;170:231-241. https://doi.org/10.1016/j.radonc.2022.02.039
  13. Deloch L, Derer A, Hueber AJ, Herrmann M, Schett GA, Wolfelschneider J, Hahn J, Ruhle PF, Stillkrieg W, Fuchs J, et al. Low-dose radiotherapy ameliorates advanced arthritis in hTNF-α tg mice by particularly positively impacting on bone metabolism. Front Immunol 2018;9:1834.
  14. Hildebrandt G, Radlingmayr A, Rosenthal S, Rothe R, Jahns J, Hindemith M, Rodel F, Kamprad F. Lowdose radiotherapy (LD-RT) and the modulation of iNOS expression in adjuvant-induced arthritis in rats. Int J Radiat Biol 2003;79:993-1001. https://doi.org/10.1080/09553000310001636639
  15. Liebmann A, Hindemith M, Jahns J, Madaj-Sterba P, Weisheit S, Kamprad F, Hildebrandt G. Low-dose X-irradiation of adjuvant-induced arthritis in rats. Efficacy of different fractionation schedules. Strahlenther Onkol 2004;180:165-172.
  16. Bauer G. Low dose radiation and intercellular induction of apoptosis: potential implications for the control of oncogenesis. Int J Radiat Biol 2007;83:873-888. https://doi.org/10.1080/09553000701727523
  17. Abdel-Aziz N, Haroun RA, Mohamed HE. Low-dose gamma radiation modulates liver and testis tissues response to acute whole body irradiation. Dose Response 2022;20:15593258221092365.
  18. Malemud CJ, Haque A, Louis NA, Wang J. Immune response and apoptosis - introduction. J Clin Cell Immunol 2012;S3:e001.
  19. Taghadosi M, Adib M, Jamshidi A, Mahmoudi M, Farhadi E. The p53 status in rheumatoid arthritis with focus on fibroblast-like synoviocytes. Immunol Res 2021;69:225-238. https://doi.org/10.1007/s12026-021-09202-7
  20. Lumniczky K, Impens N, Armengol G, Candeias S, Georgakilas AG, Hornhardt S, Martin OA, Rodel F, Schaue D. Low dose ionizing radiation effects on the immune system. Environ Int 2021;149:106212.
  21. Xin Y, Zhang HB, Tang TY, Liu GH, Wang JS, Jiang G, Zhang LZ. Low-dose radiation-induced apoptosis in human leukemia K562 cells through mitochondrial pathways. Mol Med Rep 2014;10:1569-1575. https://doi.org/10.3892/mmr.2014.2381
  22. Kern P, Keilholz L, Forster C, Seegenschmiedt MH, Sauer R, Herrmann M. In vitro apoptosis in peripheral blood mononuclear cells induced by low-dose radiotherapy displays a discontinuous dose-dependence. Int J Radiat Biol 1999;75:995-1003. https://doi.org/10.1080/095530099139755
  23. van Riel PL, Renskers L. The Disease Activity Score (DAS) and the Disease Activity Score using 28 joint counts (DAS28) in the management of rheumatoid arthritis. Clin Exp Rheumatol 2016;34:S40-S44.
  24. Kim M, Choe Y, Lee H, Jeon MG, Park JH, Noh HS, Cheon YH, Park HJ, Park J, Shin SJ, et al. Blockade of translationally controlled tumor protein attenuated the aggressiveness of fibroblast-like synoviocytes and ameliorated collagen-induced arthritis. Exp Mol Med 2021;53:67-80. https://doi.org/10.1038/s12276-020-00546-y
  25. Kim D, Kim M, Kim TW, Choe YH, Noh HS, Jeon HM, Kim H, Lee Y, Hur G, Lee KM, et al. Lymph node fibroblastic reticular cells regulate differentiation and function of CD4 T cells via CD25. J Exp Med 2022;219:e20200795.
  26. Park HJ, Jeong OY, Chun SH, Cheon YH, Kim M, Kim S, Lee SI. Butyrate improves skin/lung fibrosis and intestinal dysbiosis in bleomycin-induced mouse models. Int J Mol Sci 2021;22:2765.
  27. Hayer S, Vervoordeldonk MJ, Denis MC, Armaka M, Hoffmann M, Backlund J, Nandakumar KS, Niederreiter B, Geka C, Fischer A, et al. 'SMASH' recommendations for standardised microscopic arthritis scoring of histological sections from inflammatory arthritis animal models. Ann Rheum Dis 2021;80:714-726. https://doi.org/10.1136/annrheumdis-2020-219247
  28. Noss EH, Brenner MB. The role and therapeutic implications of fibroblast-like synoviocytes in inflammation and cartilage erosion in rheumatoid arthritis. Immunol Rev 2008;223:252-270. https://doi.org/10.1111/j.1600-065X.2008.00648.x