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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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-07-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225010934 |
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| Summary: | 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. |
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| ISSN: | 2589-0042 |