AXL and MERTK facilitate tissue repair in severe acute pancreatitis via a CCR5-dependent neutrophil and macrophage crosstalk.

IF 8.2 2区生物学 Q1 CELL BIOLOGY

Cell Communication and Signaling Pub Date : 2025-09-02 DOI:10.1186/s12964-025-02412-8

Bin Li, Xiuli Zhang, Song Liu, Xiaoyu Guo, Wanyi Lu, Kaixin Peng, Rujuan Liu, Zhigao Chen, Liang Li, Guoyong Hu, Sohail Husain, Xingpeng Wang, Li Wen

{"title":"AXL and MERTK facilitate tissue repair in severe acute pancreatitis via a CCR5-dependent neutrophil and macrophage crosstalk.","authors":"Bin Li, Xiuli Zhang, Song Liu, Xiaoyu Guo, Wanyi Lu, Kaixin Peng, Rujuan Liu, Zhigao Chen, Liang Li, Guoyong Hu, Sohail Husain, Xingpeng Wang, Li Wen","doi":"10.1186/s12964-025-02412-8","DOIUrl":null,"url":null,"abstract":"Severe acute pancreatitis (SAP) is a potentially life-threatening inflammatory disorder of the exocrine pancreas, characterized by massive cell death, which drives the progression and resolution of the disease. However, little is known about the key regulators in the tissue microenvironment that mediate tissue damage and repair. In this study, we discovered that AXL and MERTK in macrophages are responsible for tissue repair and pancreatic inflammation following SAP. Targeted deletion of Axl and Mertk in myeloid cells resulted in impaired phenotypic switch towards pro-resolving macrophage. This impairment is partly due to an accumulation of Cxcr2+ neutrophils and its interaction with Mrc1+/high macrophages likely via CCL4-CCR5 axis. Pancreatic tissue repair was effectively restored by CCR5 inhibition. Collectively, we identify a CCR5-dependent pathway orchestrated by AXL and MERTK in macrophages, which offers a pharmacological target, to promote tissue repair in SAP.","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"388"},"PeriodicalIF":8.2000,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403515/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Communication and Signaling","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s12964-025-02412-8","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Severe acute pancreatitis (SAP) is a potentially life-threatening inflammatory disorder of the exocrine pancreas, characterized by massive cell death, which drives the progression and resolution of the disease. However, little is known about the key regulators in the tissue microenvironment that mediate tissue damage and repair. In this study, we discovered that AXL and MERTK in macrophages are responsible for tissue repair and pancreatic inflammation following SAP. Targeted deletion of Axl and Mertk in myeloid cells resulted in impaired phenotypic switch towards pro-resolving macrophage. This impairment is partly due to an accumulation of Cxcr2⁺ neutrophils and its interaction with Mrc1^+/high macrophages likely via CCL4-CCR5 axis. Pancreatic tissue repair was effectively restored by CCR5 inhibition. Collectively, we identify a CCR5-dependent pathway orchestrated by AXL and MERTK in macrophages, which offers a pharmacological target, to promote tissue repair in SAP.

查看原文本刊更多论文

AXL和MERTK通过ccr5依赖性中性粒细胞和巨噬细胞串音促进严重急性胰腺炎的组织修复。

严重急性胰腺炎（SAP）是一种潜在危及生命的外分泌胰腺炎症性疾病，其特征是大量细胞死亡，这推动了疾病的进展和解决。然而，对组织微环境中介导组织损伤和修复的关键调节因子知之甚少。在这项研究中，我们发现巨噬细胞中的AXL和MERTK负责SAP后的组织修复和胰腺炎症。髓细胞中AXL和MERTK的靶向缺失导致表型向促溶解巨噬细胞的转换受损。这种损伤部分是由于Cxcr2+中性粒细胞的积累及其可能通过CCL4-CCR5轴与Mrc1+/高巨噬细胞的相互作用。抑制CCR5可有效恢复胰腺组织修复。总之，我们在巨噬细胞中发现了一个由AXL和MERTK协调的ccr5依赖通路，它提供了一个促进SAP组织修复的药理学靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cell Communication and Signaling CELL BIOLOGY-

CiteScore

11.00

自引率

0.00%

发文量

180

期刊介绍： Cell Communication and Signaling (CCS) is a peer-reviewed, open-access scientific journal that focuses on cellular signaling pathways in both normal and pathological conditions. It publishes original research, reviews, and commentaries, welcoming studies that utilize molecular, morphological, biochemical, structural, and cell biology approaches. CCS also encourages interdisciplinary work and innovative models, including in silico, in vitro, and in vivo approaches, to facilitate investigations of cell signaling pathways, networks, and behavior. Starting from January 2019, CCS is proud to announce its affiliation with the International Cell Death Society. The journal now encourages submissions covering all aspects of cell death, including apoptotic and non-apoptotic mechanisms, cell death in model systems, autophagy, clearance of dying cells, and the immunological and pathological consequences of dying cells in the tissue microenvironment.