Netrin-1 reduces lung ischemia-reperfusion injury by increasing the proportion of regulatory T cells.

Inflammation is the primary mechanism of lung ischemia-reperfusion injury (LIRI) and neurologic factors can regulate inflammatory immune responses. Netrin-1 is an axonal guidance molecule, but whether Netrin-1 plays a role in LIRI remains unclear. A mouse model of LIRI was established. Immunohistochemistry was used to detect expression of Netrin-1 and to enumerate macrophages and T cells in lung tissue. The proportion of regulatory T cells (Tregs) was assessed by flow cytometry. Levels of apoptosis were assessed by terminal deoxynucleotidyl transferase dUTP nick end staining. Numbers of macrophages and T cells in the lung tissues of mice with LIRI were elevated, while expression of netrin-1 was significantly decreased. Flow cytometry showed that the proportion of Tregs in mice with LIRI was significantly decreased. The proportion of Tregs among lymphocytes was positively correlated with netrin-1 expression. In vitro experiments showed that netrin-1 promoted an increase in Treg proportion through the A2b receptor. Animal experiments showed that netrin-1 could inhibit apoptosis and reduce T cell and macrophage infiltration by increasing the proportion of Tregs, ultimately reducing LIRI. Treg depletion using an anti-CD25 monoclonal antibody blocked the effects of netrin-1. Netrin-1 reduced LIRI by increasing the proportion of Tregs.

Citation

Zhili Chen, Yuxi Chen, Jue Zhou, Yong Li, Changyao Gong, Xiaobo Wang. Netrin-1 reduces lung ischemia-reperfusion injury by increasing the proportion of regulatory T cells. The Journal of international medical research. 2020 Jun;48(6):300060520926415

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PMID: 32485133

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