Treg cells-derived exosomes promote blood-spinal cord barrier repair and motor function recovery after spinal cord injury by delivering miR-2861
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Published:2023-10-04
Issue:1
Volume:21
Page:
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ISSN:1477-3155
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Container-title:Journal of Nanobiotechnology
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language:en
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Short-container-title:J Nanobiotechnol
Author:
Kong Guang,Xiong Wu,Li Cong,Xiao Chenyu,Wang Siming,Li Wenbo,Chen Xiangjun,Wang Juan,Chen Sheng,Zhang Yongjie,Gu Jun,Fan Jin,Jin Zhengshuai
Abstract
AbstractThe blood-spinal cord barrier (BSCB) is a physical barrier between the blood and the spinal cord parenchyma. Current evidence suggests that the disruption of BSCB integrity after spinal cord injury can lead to secondary injuries such as spinal cord edema and excessive inflammatory response. Regulatory T (Treg) cells are effective anti-inflammatory cells that can inhibit neuroinflammation after spinal cord injury, and their infiltration after spinal cord injury exhibits the same temporal and spatial characteristics as the automatic repair of BSCB. However, few studies have assessed the relationship between Treg cells and spinal cord injury, emphasizing BSCB integrity. This study explored whether Treg affects the recovery of BSCB after SCI and the underlying mechanism. We confirmed that spinal cord angiogenesis and Treg cell infiltration occurred simultaneously after SCI. Furthermore, we observed significant effects on BSCB repair and motor function in mice by Treg cell knockout and overexpression. Subsequently, we demonstrated the presence and function of exosomes in vitro. In addition, we found that Treg cell-derived exosomes encapsulated miR-2861, and miR-2861 regulated the expression of vascular tight junction (TJs) proteins. The luciferase reporter assay confirmed the negative regulation of IRAK1 by miR-2861, and a series of rescue experiments validated the biological function of IRAKI in regulating BSCB. In summary, we demonstrated that Treg cell-derived exosomes could package and deliver miR-2861 and regulate the expression of IRAK1 to affect BSCB integrity and motor function after SCI in mice, which provides novel insights for functional repair and limiting inflammation after SCI.
Funder
Suzhou key subject
Suzhou and wujiang clinical key subject, Science and Technology Development Program of Suzhou
High-level Talents of Shengze Hospital
The Suzhou National Tutorial Project
The Natural Science Foundation of China
Program for Changjiang Scholars and Innovative Research Team in University
Natural Science Foundation of Jiangsu Province for Distinguished Young Scholars
Talents project of Jiangsu Provincial People's Hospital
Publisher
Springer Science and Business Media LLC
Subject
Pharmaceutical Science,Applied Microbiology and Biotechnology,Biomedical Engineering,Molecular Medicine,Medicine (miscellaneous),Bioengineering
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