Brown adipocyte exosome - derived C22:6 inhibits the IL-1β signaling pathway to alleviate rheumatoid arthritis
IntroductionRheumatoid 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. Thi...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1543288/full |
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| author | Rui Jiang Rui Jiang Rui Jiang Yuanyuan Huang Yuanyuan Huang Rongcai Ye Rongcai Ye Yujian Zhang Yujian Zhang Meng Dong Meng Dong Hanlin Zhang Hanlin Zhang Ziyu Cheng Ziyu Cheng Zhi Zhang Zhi Zhang Jiaqi Zhang Qiaoli Zhang Gang Sun Wanzhu Jin Wanzhu Jin Wanzhu Jin |
| author_facet | Rui Jiang Rui Jiang Rui Jiang Yuanyuan Huang Yuanyuan Huang Rongcai Ye Rongcai Ye Yujian Zhang Yujian Zhang Meng Dong Meng Dong Hanlin Zhang Hanlin Zhang Ziyu Cheng Ziyu Cheng Zhi Zhang Zhi Zhang Jiaqi Zhang Qiaoli Zhang Gang Sun Wanzhu Jin Wanzhu Jin Wanzhu Jin |
| author_sort | Rui Jiang |
| collection | DOAJ |
| description | IntroductionRheumatoid 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. This study aimed to investigate the therapeutic potential of exosomes derived from human classical interscapular brown adipocytes (hcBAC-exos) in alleviating symptoms of RA in a mouse model.MethodsWe established a mouse model of collagen-induced arthritis (CIA) to evaluate the efficacy of hcBAC-exos. Specifically, we assessed the degree of RA remission by applying vitamin E emulsion, as well as a mixture of vitamin E emulsion and hcBAC-exos, to the foot paws of CIA mice. Additionally, the effects of hcBAC-exos on pro-inflammatory cytokines in macrophages (RAW264.7 cells) were investigated at the cellular level. The active components of hcBAC-exos were analyzed via lipidomics, and the mechanism of their ability to inhibit inflammation was explored.ResultsAdministration of hcBAC-exos significantly reduced the expression of pro-inflammatory cytokines in macrophages. In the CIA mouse model, transdermal application of hcBAC-exos led to notable decreases in ankle swelling and the serum levels of IL-1β and TNFα (P < 0.5). 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.DiscussionOur findings suggest that the hcBAC-exos-C22:6-TLR4-IL-1β signaling pathway plays a crucial role in the context of RA, indicating the potential clinical applications of hcBAC-exos in the treatment of inflammatory conditions such as rheumatoid arthritis. |
| format | Article |
| id | doaj-art-130033cef55f445c8d74a26b707606fb |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
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| spelling | doaj-art-130033cef55f445c8d74a26b707606fb2025-08-20T02:56:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15432881543288Brown adipocyte exosome - derived C22:6 inhibits the IL-1β signaling pathway to alleviate rheumatoid arthritisRui Jiang0Rui Jiang1Rui Jiang2Yuanyuan Huang3Yuanyuan Huang4Rongcai Ye5Rongcai Ye6Yujian Zhang7Yujian Zhang8Meng Dong9Meng Dong10Hanlin Zhang11Hanlin Zhang12Ziyu Cheng13Ziyu Cheng14Zhi Zhang15Zhi Zhang16Jiaqi Zhang17Qiaoli Zhang18Gang Sun19Wanzhu Jin20Wanzhu Jin21Wanzhu Jin22State Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology, Chinese Academy of Sciences, Beijing, ChinaThe Zhongzhou Laboratory for Integrative Biology of Henan University, Zhengzhou, Henan, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology, Chinese Academy of Sciences, Beijing, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology, Chinese Academy of Sciences, Beijing, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology, Chinese Academy of Sciences, Beijing, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology, Chinese Academy of Sciences, Beijing, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology, Chinese Academy of Sciences, Beijing, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology, Chinese Academy of Sciences, Beijing, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology, Chinese Academy of Sciences, Beijing, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing, ChinaDepartment of Gastroenterology and Hepatology, First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing, ChinaDepartment of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Gastroenterology and Hepatology, First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing, ChinaState Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology, Chinese Academy of Sciences, Beijing, ChinaThe Zhongzhou Laboratory for Integrative Biology of Henan University, Zhengzhou, Henan, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing, ChinaIntroductionRheumatoid 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. This study aimed to investigate the therapeutic potential of exosomes derived from human classical interscapular brown adipocytes (hcBAC-exos) in alleviating symptoms of RA in a mouse model.MethodsWe established a mouse model of collagen-induced arthritis (CIA) to evaluate the efficacy of hcBAC-exos. Specifically, we assessed the degree of RA remission by applying vitamin E emulsion, as well as a mixture of vitamin E emulsion and hcBAC-exos, to the foot paws of CIA mice. Additionally, the effects of hcBAC-exos on pro-inflammatory cytokines in macrophages (RAW264.7 cells) were investigated at the cellular level. The active components of hcBAC-exos were analyzed via lipidomics, and the mechanism of their ability to inhibit inflammation was explored.ResultsAdministration of hcBAC-exos significantly reduced the expression of pro-inflammatory cytokines in macrophages. In the CIA mouse model, transdermal application of hcBAC-exos led to notable decreases in ankle swelling and the serum levels of IL-1β and TNFα (P < 0.5). 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.DiscussionOur findings suggest that the hcBAC-exos-C22:6-TLR4-IL-1β signaling pathway plays a crucial role in the context of RA, indicating the potential clinical applications of hcBAC-exos in the treatment of inflammatory conditions such as rheumatoid arthritis.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1543288/fullrheumatoid arthritisexosomeC22:6TLR4IL-1β |
| spellingShingle | Rui Jiang Rui Jiang Rui Jiang Yuanyuan Huang Yuanyuan Huang Rongcai Ye Rongcai Ye Yujian Zhang Yujian Zhang Meng Dong Meng Dong Hanlin Zhang Hanlin Zhang Ziyu Cheng Ziyu Cheng Zhi Zhang Zhi Zhang Jiaqi Zhang Qiaoli Zhang Gang Sun Wanzhu Jin Wanzhu Jin Wanzhu Jin Brown adipocyte exosome - derived C22:6 inhibits the IL-1β signaling pathway to alleviate rheumatoid arthritis Frontiers in Immunology rheumatoid arthritis exosome C22:6 TLR4 IL-1β |
| title | Brown adipocyte exosome - derived C22:6 inhibits the IL-1β signaling pathway to alleviate rheumatoid arthritis |
| title_full | Brown adipocyte exosome - derived C22:6 inhibits the IL-1β signaling pathway to alleviate rheumatoid arthritis |
| title_fullStr | Brown adipocyte exosome - derived C22:6 inhibits the IL-1β signaling pathway to alleviate rheumatoid arthritis |
| title_full_unstemmed | Brown adipocyte exosome - derived C22:6 inhibits the IL-1β signaling pathway to alleviate rheumatoid arthritis |
| title_short | Brown adipocyte exosome - derived C22:6 inhibits the IL-1β signaling pathway to alleviate rheumatoid arthritis |
| title_sort | brown adipocyte exosome derived c22 6 inhibits the il 1β signaling pathway to alleviate rheumatoid arthritis |
| topic | rheumatoid arthritis exosome C22:6 TLR4 IL-1β |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1543288/full |
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