BMSC exosomes deliver JKAP to restore Th17/Treg balance via AKT/ERK, alleviating rheumatoid arthritis

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-06-06 DOI:10.1016/j.isci.2025.112832

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

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Abstract

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.

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BMSC外泌体传递JKAP，通过AKT/ERK恢复Th17/Treg平衡，缓解类风湿关节炎

JKAP调节自身免疫性疾病中的T细胞免疫和炎症。本研究探讨骨髓间充质干细胞（BMSC）衍生的外泌体如何递送JKAP以恢复类风湿关节炎（RA）中Th17/Treg的平衡。用BMSC、外泌体或jkap修饰的外泌体±AKT/ERK抑制剂治疗RA CD4+ t细胞和成纤维细胞样滑膜细胞（RA- fls）。BMSC/外泌体抑制Th17并促进Treg分化，没有外泌体的作用减弱。JKAP敲除会损害外泌体介导的Th17/Treg调节和AKT/ERK激活，而过表达会增强这些作用。jakap缺陷外泌体增加CD4+ T细胞增殖和RA-FLS炎症，AKT/ERK抑制逆转。在胶原诱导的关节炎小鼠中，外泌体缓解了症状并恢复了Th17/Treg平衡，而JKAP敲低则加重了关节炎并破坏了平衡。过表达jkap的外泌体表现出相反的效果。因此，BMSC外泌体通过AKT/ERK通路传递JKAP来恢复免疫平衡，从而减轻RA。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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