首页|A pathological joint-liver axis mediated by matrikine-activated CD4+T cells

A pathological joint-liver axis mediated by matrikine-activated CD4+T cells

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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.

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

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Department of Sports Medicine of the Second Affiliated Hospital,and Liangzhu Laboratory,Zhejiang University School of Medicine,Hangzhou,China

Dr.Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine,Zhejiang University School of Medicine,Hangzhou,China

Stomatology Hospital,School of Stomatology,Zhejiang University School of Medicine,Zhejiang Provincial Clinical Research Center for Oral Diseases,Hangzhou,China

The MOE Key Laboratory of Biosystems Homeostasis & Protection,The Key Laboratory of Cancer Molecular Cell Biology of Zhejiang Province,Life Sciences Institute,Zhejiang University,Hangzhou,China

Department of Orthopedics,Huzhou Central Hospital,Affiliated Huzhou Hospital,Zhejiang University School of Medicine,Huzhou,China

China Orthopedic Regenerative Medicine Group(CORMed),Hangzhou,China

Department of Orthopedics,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,China

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National Natural Sciences Foundation of ChinaNational Natural Sciences Foundation of ChinaNational Natural Sciences Foundation of ChinaZhejiang Provincial Natural Science Foundation of Chinapreresearch Fund project of Huzhou Central Hospital Affiliated & Zhejiang University School of Basic Medicine

T21210048239444192268203LTGY23H060009

2024

10.1038/s41392-024-01819-y

信号转导与靶向治疗(英文)

信号转导与靶向治疗(英文)

CSTPCD
ISSN：
年,卷(期)：2024.9(6)