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<p>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 <i>Axl</i> and <i>Mertk</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月2日

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  • 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

摘要

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.