Alternatively activated macrophages promote pancreatic fibrosis in chronic pancreatitis
Document Type
Journal Article
Publication Date
5-18-2015
Journal
Nature Communications
Volume
6
DOI
10.1038/ncomms8158
Abstract
© 2015 Macmillan Publishers Limited. All rights reserved. Chronic pancreatitis (CP) is a progressive and irreversible inflammatory and fibrotic disease with no cure. Unlike acute pancreatitis (AP), we find that alternatively activated macrophages (AAMs) are dominant in mouse and human CP. AAMs are dependent on interleukin (IL)-4 and IL-13 signalling, and we show that mice lacking IL-4Rα, myeloid-specific IL-4Rα and IL-4/IL-13 were less susceptible to pancreatic fibrosis. Furthermore, we demonstrate that mouse and human pancreatic stellate cells (PSCs) are a source of IL-4/IL-13. Notably, we show that pharmacologic inhibition of IL-4/IL-13 in human ex vivo studies as well as in established mouse CP decreases pancreatic AAMs and fibrosis. We identify a critical role for macrophages in pancreatic fibrosis and in turn PSCs as important inducers of macrophage-alternative activation. Our study challenges and identifies pathways involved in crosstalk between macrophages and PSCs that can be targeted to reverse or halt pancreatic fibrosis progression.
APA Citation
Xue, J., Sharma, V., Hsieh, M., Chawla, A., Murali, R., Pandol, S., & Habtezion, A. (2015). Alternatively activated macrophages promote pancreatic fibrosis in chronic pancreatitis. Nature Communications, 6 (). http://dx.doi.org/10.1038/ncomms8158