دورية أكاديمية
A pathological joint–liver axis mediated by matrikine-activated CD4+ T cells
| العنوان: | A pathological joint–liver axis mediated by matrikine-activated CD4+ T cells |
|---|---|
| المؤلفون: | Junzhi Yi, Hui Zhang, Fangyuan Bao, Zhichu Chen, Yuliang Zhong, Tianning Ye, Xuri Chen, Jingyi Qian, Mengya Tian, Min Zhu, Zhi Peng, Zongyou Pan, Jianyou Li, Zihao Hu, Weiliang Shen, Jiaqi Xu, Xianzhu Zhang, Youzhi Cai, Mengjie Wu, Hua Liu, Jing Zhou, Hongwei Ouyang |
| المصدر: | Signal Transduction and Targeted Therapy, Vol 9, Iss 1, Pp 1-15 (2024) |
| بيانات النشر: | Nature Publishing Group, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine LCC:Biology (General) |
| مصطلحات موضوعية: | Medicine, Biology (General), QH301-705.5 |
| الوصف: | Abstract The knee joint has long been considered a closed system. The pathological effects of joint diseases on distant organs have not been investigated. Herein, our clinical data showed that post-traumatic joint damage, combined with joint bleeding (hemarthrosis), exhibits a worse liver function compared with healthy control. With mouse model, hemarthrosis induces both cartilage degeneration and remote liver damage. Next, we found that hemarthrosis induces the upregulation in ratio and differentiation towards Th17 cells of CD4+ T cells in peripheral blood and spleen. Deletion of CD4+ T cells reverses hemarthrosis-induced liver damage. Degeneration of cartilage matrix induced by hemarthrosis upregulates serological type II collagen (COL II), which activates CD4+ T cells. Systemic application of a COL II antibody blocks the activation. Furthermore, bulk RNAseq and single-cell qPCR analysis revealed that the cartilage Akt pathway is inhibited by blood treatment. Intra-articular application of Akt activator blocks the cartilage degeneration and thus protects against the liver impairment in mouse and pig models. Taken together, our study revealed a pathological joint–liver axis mediated by matrikine-activated CD4+ T cells, which refreshes the organ-crosstalk axis and provides a new treatment target for hemarthrosis-related disease. Intra-articular bleeding induces cartilage degradation through down-reulation of cartilage Akt pathway. During this process, the soluble COL II released from the damaged cartilage can activate peripheral CD4+ T cells, differention into Th17 cells and secretion of IL-17, which consequently induces liver impairment. Intra-articular application of sc79 (inhibitor of Akt pathway) can prevent the cartilage damage as well as its peripheral influences. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2059-3635 |
| Relation: | https://doaj.org/toc/2059-3635 |
| DOI: | 10.1038/s41392-024-01819-y |
| URL الوصول: | https://doaj.org/article/4cd22904ee3f49ceae3c123f059f051a |
| رقم الأكسشن: | edsdoj.4cd22904ee3f49ceae3c123f059f051a |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 20593635 |
|---|---|
| DOI: | 10.1038/s41392-024-01819-y |