Publication Date
9-1-2023
Journal
Nature Immunology
DOI
10.1038/s41590-023-01579-x
PMID
37563309
PMCID
PMC10757749
PubMedCentral® Posted Date
12-31-2023
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Keywords
Mice, Animals, Pancreas, Macrophages, Pancreatitis, Fibrosis, Pancreatic Neoplasms
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.
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