BMSC exosomes deliver JKAP to restore Th17/Treg balance via AKT/ERK, alleviating rheumatoid arthritis
Summary: JKAP regulates T cell immunity and inflammation in autoimmune diseases. This study investigates how bone marrow mesenchymal stem cell (BMSC)-derived exosomes deliver JKAP to restore Th17/Treg balance in rheumatoid arthritis (RA). RA CD4+ T-cells and fibroblast-like synoviocytes (RA-FLS) wer...
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| Language: | English |
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Elsevier
2025-07-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225010934 |
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| author | Fang-Tian Xu Yu Ling Hui-Xian Wei Lingzhang Meng Dong Yin Zhong-Hong Lai Yu Huang Xiao Huang Hai-Ye Li Qin-Wen Luo Jian Song Qiang Tang Hong-Mian Li |
| author_facet | Fang-Tian Xu Yu Ling Hui-Xian Wei Lingzhang Meng Dong Yin Zhong-Hong Lai Yu Huang Xiao Huang Hai-Ye Li Qin-Wen Luo Jian Song Qiang Tang Hong-Mian Li |
| author_sort | Fang-Tian Xu |
| collection | DOAJ |
| description | Summary: JKAP regulates T cell immunity and inflammation in autoimmune diseases. This study investigates how bone marrow mesenchymal stem cell (BMSC)-derived exosomes deliver JKAP to restore Th17/Treg balance in rheumatoid arthritis (RA). RA CD4+ T-cells and fibroblast-like synoviocytes (RA-FLS) were treated with BMSC, exosomes, or JKAP-modified exosomes ± AKT/ERK inhibitors. BMSC/exosomes suppressed Th17 and promoted Treg differentiation, effects diminished without exosomes. JKAP knockdown impaired exosome-mediated Th17/Treg regulation and AKT/ERK activation, while overexpression enhanced these effects. JKAP-deficient exosomes increased CD4+ T cell proliferation and RA-FLS inflammation, reversed by AKT/ERK inhibition. In collagen-induced arthritis mice, exosomes alleviated symptoms and restored Th17/Treg balance, whereas JKAP knockdown exacerbated arthritis and disrupted balance. JKAP-overexpressing exosomes showed opposite effects. Thus, BMSC exosomes mitigate RA by delivering JKAP to restore immune balance via AKT/ERK pathways. |
| format | Article |
| id | doaj-art-22e472a9868d44eba5598a045aeee47b |
| institution | DOAJ |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-22e472a9868d44eba5598a045aeee47b2025-08-20T02:42:15ZengElsevieriScience2589-00422025-07-0128711283210.1016/j.isci.2025.112832BMSC exosomes deliver JKAP to restore Th17/Treg balance via AKT/ERK, alleviating rheumatoid arthritisFang-Tian Xu0Yu Ling1Hui-Xian Wei2Lingzhang Meng3Dong Yin4Zhong-Hong Lai5Yu Huang6Xiao Huang7Hai-Ye Li8Qin-Wen Luo9Jian Song10Qiang Tang11Hong-Mian Li12Department of Orthopedics, The First Affiliated Hospital of Gannan Medical University, Ganzhou, ChinaDepartment of Emergency, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China; Department of Emergency, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Key Laboratory of Biomedical Material Research of Guangxi (Cultivation), Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China; Burn Plastic & Trauma Surgery Department, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China; Department of Orthopedics, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Institute of Cardiovascular Medicine, Guangxi Academy of Medical Sciences & The Guangxi Academy of Medical Sciences, Nanning, China; Research Center of Medical Sciences, Department of Plastic and Aesthetic Surgery, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region & Research Center of Medical Sciences, Nanning, China; Department of Orthopedics, The Ninth People's Hospital of Nanning, Binyang, China; Department of Plastic and Aesthetic Surgery & Research Center of Medical Sciences, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaInstitute of Cardiovascular Medicine, Guangxi Academy of Medical Sciences & The Guangxi Academy of Medical Sciences, Nanning, ChinaDepartment of Orthopedics, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Gannan Medical University, Ganzhou, ChinaDepartment of Orthopedics, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Orthopedics, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China; Department of Emergency, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Key Laboratory of Biomedical Material Research of Guangxi (Cultivation), Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China; Burn Plastic & Trauma Surgery Department, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China; Department of Orthopedics, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Institute of Cardiovascular Medicine, Guangxi Academy of Medical Sciences & The Guangxi Academy of Medical Sciences, Nanning, China; Research Center of Medical Sciences, Department of Plastic and Aesthetic Surgery, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region & Research Center of Medical Sciences, Nanning, China; Department of Orthopedics, The Ninth People's Hospital of Nanning, Binyang, China; Department of Plastic and Aesthetic Surgery & Research Center of Medical Sciences, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China; Department of Emergency, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Key Laboratory of Biomedical Material Research of Guangxi (Cultivation), Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China; Burn Plastic & Trauma Surgery Department, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China; Department of Orthopedics, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Institute of Cardiovascular Medicine, Guangxi Academy of Medical Sciences & The Guangxi Academy of Medical Sciences, Nanning, China; Research Center of Medical Sciences, Department of Plastic and Aesthetic Surgery, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region & Research Center of Medical Sciences, Nanning, China; Department of Orthopedics, The Ninth People's Hospital of Nanning, Binyang, China; Department of Plastic and Aesthetic Surgery & Research Center of Medical Sciences, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaInstitute of Cardiovascular Medicine, Guangxi Academy of Medical Sciences & The Guangxi Academy of Medical Sciences, Nanning, China; Corresponding authorKey Laboratory of Biomedical Material Research of Guangxi (Cultivation), Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China; Corresponding authorDepartment of Emergency, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Research Center of Medical Sciences, Department of Plastic and Aesthetic Surgery, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region & Research Center of Medical Sciences, Nanning, China; Corresponding authorSummary: JKAP regulates T cell immunity and inflammation in autoimmune diseases. This study investigates how bone marrow mesenchymal stem cell (BMSC)-derived exosomes deliver JKAP to restore Th17/Treg balance in rheumatoid arthritis (RA). RA CD4+ T-cells and fibroblast-like synoviocytes (RA-FLS) were treated with BMSC, exosomes, or JKAP-modified exosomes ± AKT/ERK inhibitors. BMSC/exosomes suppressed Th17 and promoted Treg differentiation, effects diminished without exosomes. JKAP knockdown impaired exosome-mediated Th17/Treg regulation and AKT/ERK activation, while overexpression enhanced these effects. JKAP-deficient exosomes increased CD4+ T cell proliferation and RA-FLS inflammation, reversed by AKT/ERK inhibition. In collagen-induced arthritis mice, exosomes alleviated symptoms and restored Th17/Treg balance, whereas JKAP knockdown exacerbated arthritis and disrupted balance. JKAP-overexpressing exosomes showed opposite effects. Thus, BMSC exosomes mitigate RA by delivering JKAP to restore immune balance via AKT/ERK pathways.http://www.sciencedirect.com/science/article/pii/S2589004225010934ImmunologyImmunityCell biology |
| spellingShingle | Fang-Tian Xu Yu Ling Hui-Xian Wei Lingzhang Meng Dong Yin Zhong-Hong Lai Yu Huang Xiao Huang Hai-Ye Li Qin-Wen Luo Jian Song Qiang Tang Hong-Mian Li BMSC exosomes deliver JKAP to restore Th17/Treg balance via AKT/ERK, alleviating rheumatoid arthritis iScience Immunology Immunity Cell biology |
| title | BMSC exosomes deliver JKAP to restore Th17/Treg balance via AKT/ERK, alleviating rheumatoid arthritis |
| title_full | BMSC exosomes deliver JKAP to restore Th17/Treg balance via AKT/ERK, alleviating rheumatoid arthritis |
| title_fullStr | BMSC exosomes deliver JKAP to restore Th17/Treg balance via AKT/ERK, alleviating rheumatoid arthritis |
| title_full_unstemmed | BMSC exosomes deliver JKAP to restore Th17/Treg balance via AKT/ERK, alleviating rheumatoid arthritis |
| title_short | BMSC exosomes deliver JKAP to restore Th17/Treg balance via AKT/ERK, alleviating rheumatoid arthritis |
| title_sort | bmsc exosomes deliver jkap to restore th17 treg balance via akt erk alleviating rheumatoid arthritis |
| topic | Immunology Immunity Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225010934 |
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