2. Academic Validation
  3. Dihydroartemisinin alleviates erosive bone destruction by modifying local Treg cells in inflamed joints: A novel role in the treatment of rheumatoid arthritis

Dihydroartemisinin alleviates erosive bone destruction by modifying local Treg cells in inflamed joints: A novel role in the treatment of rheumatoid arthritis

  • Int Immunopharmacol. 2024 Mar 5:130:111795. doi: 10.1016/j.intimp.2024.111795.
Xiaoxue Cao 1,  Zhaoran Wang 2,  Yi Jiao 3,  Wenya Diao 4,  Qishun Geng 5,  Lu Zhao 6,  Zihan Wang 7,  Xing Wang 8,  Mengxiao Zhang 9,  Jiahe Xu 10,  Bailiang Wang 11,  Tingting Deng 12,  Cheng Xiao 13
Affiliations

Affiliations

  • 1 Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing, China; Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China. Electronic address: snowcxx93@student.pumc.edu.cn.
  • 2 Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing, China; Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China. Electronic address: b2023023018@pumc.edu.cn.
  • 3 China-Japan Friendship Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China. Electronic address: 20220941348@bucm.edu.cn.
  • 4 China-Japan Friendship Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China. Electronic address: 20230941361@bucm.edu.cn.
  • 5 Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing, China; Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China. Electronic address: zrgengqs@student.pumc.edu.cn.
  • 6 China-Japan Friendship Hospital, Capital Medical University, Beijing, China. Electronic address: zhaolu@mail.ccmu.edu.cn.
  • 7 China-Japan Friendship Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China. Electronic address: 20220941353@bucm.edu.cn.
  • 8 China-Japan Friendship Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China. Electronic address: 20210941326@bucm.edu.cn.
  • 9 Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing, China. Electronic address: a11232023@163.com.
  • 10 China-Japan Friendship School of Clinical Medicine, Peking University, Beijing, China. Electronic address: 2311210688@pku.edu.cn.
  • 11 Department of Orthopaedic Surgery, China-Japan Friendship Hospital, Beijing, China. Electronic address: wangbailiang@zryhyy.com.cn.
  • 12 Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing, China. Electronic address: dengtingting@zryhyy.com.cn.
  • 13 Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing, China; Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China; Department of Emergency, China-Japan Friendship Hospital, Beijing, China. Electronic address: xiaocheng@zryhyy.com.cn.
PMID: 38447418 DOI: 10.1016/j.intimp.2024.111795
Abstract

Treg cell-based therapy has exhibited promising efficacy in combatting rheumatoid arthritis (RA). Dihydroartemisinin (DHA) exerts broad immunomodulatory effects across various diseases, with its recent spotlight on T-cell regulation in autoimmune conditions. The modulation of DHA on Treg cells and its therapeutic role in RA has yet to be fully elucidated. This study seeks to unveil the influence of DHA on Treg cells in RA and furnish innovative substantiation for the potential of DHA to ameliorate RA. To this end, we initially scrutinized the impact of DHA-modulated Treg cells on osteoclast (OC) formation in vitro using Treg cell-bone marrow-derived monocyte (BMM) coculture systems. Subsequently, employing the collagen-induced arthritis (CIA) rat model, we validated the efficacy of DHA and probed its influence on Treg cells in the spleen and popliteal lymph nodes (PLN). Finally, leveraging deep proteomic analysis with data-independent acquisition (DIA) and parallel accumulation-serial fragmentation (PASEF) technology, we found the alterations in the Treg cell proteome in PLN by proteomic analysis. Our findings indicate that DHA augmented suppressive Treg cells, thereby impeding OC formation in vitro. Consistently, DHA mitigated erosive joint destruction and osteoclastogenesis by replenishing splenic and joint-draining lymph node Treg cells in CIA rats. Notably, DHA induced alterations in the Treg cell proteome in PLN, manifesting distinct upregulation of alloantigen Col2a1 (Type II collagen alfa 1 chain) and CD8a (T-cell surface glycoprotein CD8 alpha chain) in Treg cells, signifying DHA's targeted modulation of Treg cells, rendering them more adept at sustaining immune tolerance and impeding bone erosion. These results unveil a novel facet of DHA in the treatment of RA.

Keywords

DIA-PASEF technology; Dihydroartemisinin; Erosive bone destruction; Rheumatoid arthritis; Treg cell; Treg cell-BMM coculture system.

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