Figure 2.

Signaling driving a macrophage phenotype switch and lesion progression. ADM lesions consist of duct-like cells that originated from acinar cells as well as a small fraction of DCLK1 positive (DCLK1+) cells that originate from duct-like cells. Both, DCLK1+ cells and duct-like cells (but to a lesser degree) secrete IL-13, which induces a polarization switch in macrophages from an inflammatory to an alternatively-activated M2 phenotype. Resulting cells express M2a markers and induce lesion cell proliferation via secretion of IL-1ra, CCL2 and TIMP1, and induce fibrosis by activating pancreatic stellate cells (PSCs) via TGFβ. PanIN lesion cells also produce CCL2 which can act auto-stimulatory to enhance lesion growth, but also serves as a chemoattractant for peritoneal macrophages or monocytes. Created with BioRender.com.