IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1

Jenkins, Stephen J., Ruckerl, Dominik, Thomas, Graham D., Hewitson, James P., Duncan, Sheelagh, Brombacher, Frank, Maizels, Rick M., Hume, David A. and Allen, Judith E. (2013) IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1. Journal of Experimental Medicine, 210 11: 2477-2491. doi:10.1084/jem.20121999


Author Jenkins, Stephen J.
Ruckerl, Dominik
Thomas, Graham D.
Hewitson, James P.
Duncan, Sheelagh
Brombacher, Frank
Maizels, Rick M.
Hume, David A.
Allen, Judith E.
Title IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1
Journal name Journal of Experimental Medicine   Check publisher's open access policy
ISSN 0022-1007
1540-9538
Publication date 2013-10-07
Sub-type Article (original research)
DOI 10.1084/jem.20121999
Open Access Status Not yet assessed
Volume 210
Issue 11
Start page 2477
End page 2491
Total pages 15
Place of publication New York, NY, United States
Publisher Rockefeller University Press
Language eng
Formatted abstract
Macrophages (Mφs) colonize tissues during inflammation in two distinct ways: recruitment of monocyte precursors and proliferation of resident cells. We recently revealed a major role for IL-4 in the proliferative expansion of resident Mφs during a Th2-biased tissue nematode infection. We now show that proliferation of Mφs during intestinal as well as tissue nematode infection is restricted to sites of IL-4 production and requires Mφ-intrinsic IL-4R signaling. However, both IL-4Rα-dependent and -independent mechanisms contributed to Mφ proliferation during nematode infections. IL-4R-independent proliferation was controlled by a rise in local CSF-1 levels, but IL-4Rα expression conferred a competitive advantage with higher and more sustained proliferation and increased accumulation of IL-4Rα+ compared with IL-4Rα- cells. Mechanistically, this occurred by conversion of IL-4Rα+ Mφs from a CSF-1-dependent to -independent program of proliferation. Thus, IL-4 increases the relative density of tissue Mφs by overcoming the constraints mediated by the availability of CSF-1. Finally, although both elevated CSF1R and IL-4Rα signaling triggered proliferation above homeostatic levels, only CSF-1 led to the recruitment of monocytes and neutrophils. Thus, the IL-4 pathway of proliferation may have developed as an alternative to CSF-1 to increase resident Mφ numbers without coincident monocyte recruitment.
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID BB/H012559/1
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Mater Research Institute-UQ (MRI-UQ)
 
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Created: Fri, 20 Apr 2018, 09:29:30 EST