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

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

  • Cell Commun Signal. 2025 Sep 2;23(1):388. doi: 10.1186/s12964-025-02412-8.
Bin Li 1,  Xiuli Zhang 2 3,  Song Liu 4,  Xiaoyu Guo 2,  Wanyi Lu 2,  Kaixin Peng 2 3,  Rujuan Liu 2,  Zhigao Chen 2,  Liang Li 1,  Guoyong Hu 1,  Sohail Husain 5,  Xingpeng Wang 6,  Li Wen 7
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 Center for Biomarker Discovery and Validation, National Infrastructures for Translational Medicine (PUMCH), Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
  • 3 Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
  • 4 Center for Bioinformatics, National Infrastructures for Translational Medicine (PUMCH), Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
  • 5 Division of Pediatric Gastroenterology, Department of Pediatrics, Stanford University, Palo Alto, CA, USA.
  • 6 Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. richardwangxp@163.com.
  • 7 Center for Biomarker Discovery and Validation, National Infrastructures for Translational Medicine (PUMCH), Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China. wenli7007@gmail.com.
PMID: 40898178 DOI: 10.1186/s12964-025-02412-8
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.

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