组织驻留巨噬细胞（TRMs）是长寿命细胞，能够在局部维持并与从单核细胞分化而来的巨噬细胞表型有所不同。TRMs和单核细胞来源的巨噬细胞在不同病理情况下是否具有不同的功能尚不清楚。在这里，我们展示了在小鼠胰腺炎和胰腺癌中积累的大量巨噬细胞是从TRMs扩张而来的。胰腺TRMs具有重要的细胞外基质重塑表型，在炎症期间对维持组织稳态起重要作用。TRMs的丧失导致严重胰腺炎的恶化和死亡，原因是因为泡状细胞的存活和恢复受损。在胰腺炎期间，TRMs通过诱导成纤维细胞的积累和激活发挥保护作用，这对于初始纤维化作为创伤愈合反应是必要的。然而，相同的TRM驱动纤维化是胰腺癌发病和进展的推动因素。综上所述，这些发现表明TRMs通过调节间质生成在胰腺炎和癌症发病机制中发挥不同的作用。© 2023作者专有许可Springer Nature America, Inc。

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.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.