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Updated: Jul 19, 2025
Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
Fibrosis induced by resident macrophages has divergent roles in pancreas inflammatory injury and PDAC
John M Baer1, Chong Zuo1, Liang-I Kang2
1Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Abstract:
Tissue-resident macrophages (TRMs) are long-lived cells that maintain locally and can be phenotypically distinct from monocyte-derived macrophages. Whether TRMs and monocyte-derived macrophages have district roles under differing pathologies is not understood. Here, we showed that a substantial portion of the macrophages that accumulated during pancreatitis and pancreatic cancer in mice had expanded from TRMs. Pancreas TRMs had an extracellular matrix remodeling phenotype that was important for maintaining tissue homeostasis during inflammation. Loss of TRMs led to exacerbation of severe pancreatitis and death, due to impaired acinar cell survival and recovery. During pancreatitis, TRMs elicited protective effects by triggering the accumulation and activation of fibroblasts, which was necessary for initiating fibrosis as a wound healing response. The same TRM-driven fibrosis, however, drove pancreas cancer pathogenesis and progression. Together, these findings indicate that TRMs play divergent roles in the pathogenesis of pancreatitis and cancer through regulation of stromagenesis.
Insights
Tissue-resident macrophages (TRMs) are key players in pancreatic inflammation and cancer. These cells protect against pancreatitis but promote cancer progression by regulating fibrosis.
Area of Science:
- Immunology
- Gastroenterology
- Oncology
Background:
- Tissue-resident macrophages (TRMs) are distinct from monocyte-derived macrophages and play crucial roles in tissue homeostasis.
- The specific roles of TRMs versus monocyte-derived macrophages in pancreatic pathologies remain unclear.
Purpose of the Study:
- To investigate the origin and function of macrophages in pancreatitis and pancreatic cancer.
- To elucidate the distinct roles of TRMs in these distinct pancreatic diseases.
Main Methods:
- Utilized mouse models of pancreatitis and pancreatic cancer.
- Analyzed macrophage populations and their phenotypes.
- Investigated the impact of TRM depletion on disease progression.
Main Results:
- Macrophages accumulating in pancreatitis and pancreatic cancer largely originated from expanded TRMs.
- Pancreatic TRMs exhibit an extracellular matrix remodeling phenotype crucial for tissue homeostasis during inflammation.
- Loss of TRMs exacerbated pancreatitis, impairing acinar cell survival and recovery.
- TRMs initiated protective fibrosis during pancreatitis but this same fibrosis drove pancreatic cancer progression.
- TRMs regulate stromagenesis, influencing both pancreatitis and cancer pathogenesis.
Conclusions:
- TRMs play divergent roles in pancreatitis and pancreatic cancer.
- TRM-mediated fibrosis is protective in pancreatitis but pathogenic in pancreatic cancer.
- TRMs are critical regulators of pancreatic stromagenesis with context-dependent roles in disease.
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