Journal Article

The effect of TIM1+ Breg cells in liver ischemia-reperfusion injury

Yang, Beng, Zhou, Jie, Ren, Shenli, Zhang, Yu, Zhang, Cheng, Hu, Zhenhua, Peng, Chuanhui

2025

Overview

Liver transplantation is the only effective method for end-stage liver disease; however, liver ischemia reperfusion injury (IRI) seriously affects donor liver function after liver transplantation. IRI is a pathophysiological process in which organ damage is aggravated after the blood flow and oxygen supply of ischemic organ tissues are restored. It combines the two stages of hypoxic cell stress triggered by ischemia and inflammation-mediated reperfusion injury. Herein, we studied the protective effect and mechanism of the anti-T cell Ig and mucin domain (TIM1) monoclonal antibody, RMT1-10, on hepatic cell injury induced by IRI. First, a liver IRI model was established in vivo. HE, TEM, and Tunel were used to detect liver tissue injury, changes in the liver ultrastructure and liver cell apoptosis, respectively. ELISA were performed to determine the levels of ALT, AST, MDA, GSH, and related inflammatory factors. We found that RMT1-10 could significantly reduce liver injury. Flow cytometry results showed that the number of TIM1 + regulatory B cells (Bregs) in the IRI liver increased briefly, while pretreatment with RMT1-10 could increase the number of TIM1 + Bregs and interleukin-10 (IL-10) secretion in liver IRI model mice, thus playing a protective role in liver reperfusion. When Anti-CD20 was used to remove B cells, RMT1-10 had a reduced effect on liver IRI. Previous data showed that the number of T helper 1 cells (Th1:CD4 + ; CD8 + ) increased significantly after IRI. RMT1-10 inhibited Th1 cells; however, it significantly activated regulatory T cells. Sequencing analysis showed that RMT1-10 could significantly downregulate the expression of nuclear factor-kappa B (NF-κB) pathway-related genes induced by IRI. These results suggested that RMT1-10 could promote the maturation of B cells through an atypical NF-κB pathway, thereby increasing the number of TIM1 + Bregs and associated IL-10 secretion to regulate the inflammatory response, thereby protecting against liver IRI.

• Publisher: Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
• Subject: 13/2 / 13/31 / 631/80 / 692/699 / Animal models / Animals / Antibodies / Apoptosis / Apoptosis - drug effects / B-Lymphocytes, Regulatory - immunology / B-Lymphocytes, Regulatory - metabolism / Biochemistry / Biomedical and Life Sciences / Blood flow / CD20 antigen / CD4 antigen / CD8 antigen / Cell Biology / Cell Culture / Cell injury / Cellular stress response / Disease Models, Animal / Flow cytometry / Hepatitis A Virus Cellular Receptor 1 - immunology / Hepatitis A Virus Cellular Receptor 1 - metabolism / Hepatocytes / Hypoxia / Immunoglobulins / Immunology / Immunoregulation / Inflammation / Interleukin 10 / Interleukin-10 - metabolism / Ischemia / Life Sciences / Liver - metabolism / Liver - pathology / Liver diseases / Liver transplantation / Liver transplants / Lymphocytes B / Lymphocytes T / Male / Mice / Mice, Inbred C57BL / Monoclonal antibodies / NF-κB protein / Reperfusion / Reperfusion Injury - immunology / Reperfusion Injury - metabolism / Reperfusion Injury - pathology / Sequence analysis / Ultrastructure