eLife
eLife
5 years ago

Epithelial-Myeloid cell crosstalk regulates acinar cell plasticity and pancreatic remodeling in mice

Arthur Brannon, Wei Yan, Yaqing Zhang, Esha Mathew, Alekya Vinta, Kevin T Kane, Howard C Crawford, Maeva Adoumie, Marina Pasca di Magliano
Dedifferentiation of acini to duct-like cells occurs during the physiologic damage response in the pancreas, but this process can be co-opted by oncogenic Kras to drive carcinogenesis. Myeloid cells infiltrate the pancreas during the onset of pancreatic cancer, and promote carcinogenesis. Here, we show that the function of infiltrating myeloid cells is regulated by oncogenic Kras expressed in epithelial cells. In the presence of oncogenic Kras, myeloid cells promote acinar dedifferentiation and carcinogenesis. Upon inactivation of oncogenic Kras, myeloid cells promote re-differentiation of acinar cells, remodeling of the fibrotic stroma and tissue repair. Intriguingly, both aspects of myeloid cell activity depend, at least in part, on activation of EGFR/MAPK signaling, with different subsets of ligands and receptors in different target cells promoting carcinogenesis or repair, respectively. Thus, the cross-talk between epithelial cells and infiltrating myeloid cells determines the balance between tissue repair and carcinogenesis in the pancreas.

Publisher URL: https://elifesciences.org/articles/27388

DOI: 10.7554/eLife.27388

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