| First Author | Jenkins SJ | Year | 2013 |
| Journal | J Exp Med | Volume | 210 |
| Issue | 11 | Pages | 2477-91 |
| PubMed ID | 24101381 | Mgi Jnum | J:204583 |
| Mgi Id | MGI:5532855 | Doi | 10.1084/jem.20121999 |
| Citation | Jenkins SJ, et al. (2013) IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1. J Exp Med 210(11):2477-91 |
| abstractText | Macrophages (MPhis) 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 MPhis during a Th2-biased tissue nematode infection. We now show that proliferation of MPhis during intestinal as well as tissue nematode infection is restricted to sites of IL-4 production and requires MPhi-intrinsic IL-4R signaling. However, both IL-4Ralpha-dependent and -independent mechanisms contributed to MPhi proliferation during nematode infections. IL-4R-independent proliferation was controlled by a rise in local CSF-1 levels, but IL-4Ralpha expression conferred a competitive advantage with higher and more sustained proliferation and increased accumulation of IL-4Ralpha(+) compared with IL-4Ralpha(-) cells. Mechanistically, this occurred by conversion of IL-4Ralpha(+) MPhis from a CSF-1-dependent to -independent program of proliferation. Thus, IL-4 increases the relative density of tissue MPhis by overcoming the constraints mediated by the availability of CSF-1. Finally, although both elevated CSF1R and IL-4Ralpha 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 MPhi numbers without coincident monocyte recruitment. |
