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Cited by 362

The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.

Alternatively activated macrophages promote pancreatic fibrosis in chronic pancreatitis

Open access
Xue, Jing, Sharma, Vishal, Hsieh, Michael H., Chawla, Ajay, Murali, Ramachandran, Pandol, Stephen J., Habtezion, Aida·2015·Nature Communications
DOI 10.1038/ncomms8158
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Abstract

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. Chronic pancreatitis is an inflammatory disease accompanied by fibrosis. Here the authors show that pancreatic stellate cells produce IL-4 and IL-13 that trigger alternative activation of macrophages, and that genetic or pharmacological inhibition of IL-4/IL-13 signaling ameliorates the disease.

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Metadata

Authors
Xue, J., Sharma, V., Hsieh, M. H., Chawla, A., Murali, R., Pandol, S. J., & Habtezion, A.
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2015-05-18
Volume
6
Issue
1
Pages
7158-7158
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/ncomms8158
OpenAlex
W335152085
Cited by
362
References
42
FWCI
25.15
Type
journal article
Language
en
Open access
gold

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