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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1
Journal of Experimental Medicine, Volume 210, No. 11, Year 2013
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Description
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. © 2013 Jenkins et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3804948/bin/supp_210_11_2477__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC3804948/bin/supp_jem.20121999_JEM_20121999_sm.pdf
Authors & Co-Authors
Jenkins, Stephen J.
United Kingdom, Edinburgh
The University of Edinburgh
United Kingdom, Edinburgh
University of Edinburgh, College of Medicine and Veterinary Medicine
Rückerl, Dominik
United Kingdom, Edinburgh
The University of Edinburgh
Thomas, Graham D.
United Kingdom, Edinburgh
The University of Edinburgh
Hewitson, James P.
United Kingdom, Edinburgh
The University of Edinburgh
Duncan, Sheelagh
United Kingdom, Edinburgh
The University of Edinburgh
Brombacher, Frank
South Africa, Cape Town
University of Cape Town
Maizels, Rick M.
United Kingdom, Edinburgh
The University of Edinburgh
Hume, David A.
United Kingdom, Edinburgh
University of Edinburgh, College of Medicine and Veterinary Medicine
Allen, Judith E.
United Kingdom, Edinburgh
The University of Edinburgh
Statistics
Citations: 356
Authors: 9
Affiliations: 3
Identifiers
Doi:
10.1084/jem.20121999
ISSN:
00221007
e-ISSN:
15409538