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IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2013 Oct 21; Vol. 210 (11), pp. 2477-91. Date of Electronic Publication: 2013 Oct 07. - Publication Year :
- 2013
-
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.
- Subjects :
- Adaptive Immunity immunology
Animals
Cell Proliferation
Filarioidea physiology
Heligmosomatoidea physiology
Inflammation parasitology
Inflammation pathology
Intestines immunology
Intestines parasitology
Intestines pathology
Macrophage Activation
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Neutrophils metabolism
Receptor, Macrophage Colony-Stimulating Factor metabolism
Receptors, Interleukin-4 metabolism
Homeostasis
Interleukin-4 metabolism
Macrophage Colony-Stimulating Factor metabolism
Macrophages cytology
Macrophages metabolism
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 1540-9538
- Volume :
- 210
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 24101381
- Full Text :
- https://doi.org/10.1084/jem.20121999