ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1543288
Brown adipocyte exosome -derived C22:6 inhibits the IL-1β signaling pathway to alleviate rheumatoid arthritis
Provisionally accepted
Rui Jiang1,2
Yuanyuan Huang1,2
Rongcai Ye1,2
Yujian Zhang1,2Meng Dong1,2Hanlin Zhang1,2Ziyu Cheng1,2
Zhi Zhang1,2Jiaqi Zhang3
Qiaoli Zhang4*
Gang Sun3*
Wanzhu Jin1,2,5*- 1Institute of Zoology, Chinese Academy of Sciences (CAS), Beijing, Beijing Municipality, China
- 2Chinese Academy of Sciences (CAS), Beijing, Beijing, China
- 3Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, Beijing Municipality, China
- 4Department of Obstetrics and Gynecology, Peking Union Medical College Hospital (CAMS), Beijing, Beijing Municipality, China
- 5The Zhongzhou Laboratory for Integrative Biology, Zhengzhou, China
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Rheumatoid arthritis (RA) is an autoimmune disorder characterized by significant disability and teratogenic effects, for which there are few effective curative therapies. Exosomes derived from mesenchymal stem cells (MSCs) exhibit anti-inflammatory and tissue regenerative properties. In the current study, we investigated the transdermal effects of exosomes from human classical interscapular brown adipocytes (hcBAC-exos) in the context of RA mice model. Our findings indicated that hcBACexos markedly reduced the expression of pro-inflammatory cytokines in macrophages (RAW264.7 cells). Furthermore, in a collagen-induced arthritis (CIA) mouse model, transdermal administration of hcBAC-exos resulted in a significant reduction in ankle swelling and serum levels of IL-1β and TNFα, suggesting their therapeutic potential for alleviating RA symptoms. Mechanistically, lipidomic analysis showed that Docosahexaenoic acid (C22:6) is highly enriched in hcBAC-exos. Furthermore, we found that C22:6 specifically inhibits IL-1β expression by binding to the amino acids Y183, S210, E265, S182, and R223 of TLR4, mutating these amino acids results in the loss of C22:6 binding activity to TLR4. Taken together, we demonstrated that the hcBAC-exos-C22:6-TLR4-IL-1β signaling pathway plays an important role in the context of RA and suggests potential clinical applications.
Keywords: Rheumatoid arthritis, exosome, C22:6, TLR4, IL-1β
Received: 11 Dec 2024; Accepted: 17 Apr 2025.
Copyright: © 2025 Jiang, Huang, Ye, Zhang, Dong, Zhang, Cheng, Zhang, Zhang, Zhang, Sun and Jin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Qiaoli Zhang, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital (CAMS), Beijing, 100730, Beijing Municipality, China
Gang Sun, Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, 100853, Beijing Municipality, China
Wanzhu Jin, Institute of Zoology, Chinese Academy of Sciences (CAS), Beijing, 100101, Beijing Municipality, China
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