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

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<sup>+</sup> neutrophils and its interaction with Mrc1<sup>+/high</sup> 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.

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Publication Details

Journal
Cell Communication and Signaling
Published
2025-09-02
DOI
https://doi.org/10.1186/s12964-025-02412-8
Primary Topic
Phagocytosis and Immune Regulation
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Sohail Z. Husain, Guoyong Hu, Xingpeng Wang, Ru‐Juan Liu et al.
Cell Communication and Signaling
Phagocytosis and Immune Regulation
article

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

Sohail Z. Husain, Guoyong Hu, Xingpeng Wang, Ru‐Juan Liu, Wen Li, Song Liu, Xiuli Zhang, Bin Li, Liang Li, Zhigao Chen, Xiaoyu Guo, Wanyi Lu, Kaixin Peng
article en

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<sup>+</sup> neutrophils and its interaction with Mrc1<sup>+/high</sup> 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.

Cell Communication and SignalingVol. 23(1)
Palo Alto University (US), Shanghai Jiao Tong University (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Peking Union Medical College Hospital (CN), Shanghai First People's Hospital (CN), Stanford Medicine (US), Stanford University (US)
Yale University, Natural Science Foundation of Shanghai, National Natural Science Foundation of China, Peking Union Medical College Hospital
Openalex Percentile: Top 75%
Phagocytosis and Immune Regulation
DOIOpen Access PDFOpenAlex
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