Macrophage-Specific ErbB4 is Induced by DSS Colitis and Regulates Macrophage Survival

The ErbB4 receptor tyrosine kinase is induced in the colonic epithelium in inflammatory bowel disease (IBD), and the ErbB4-specific ligand neuregulin-4 is protective in murine colitis models. Interestingly, ErbB4 is also robustly detectable in the submucosal stroma where immune cells accumulate during inflammation. Previous studies have shown ErbB4 expression on circulating human monocytes and neuronal macrophages (Mo), but its expression on intestinal Mo and role in Mo biology are unknown. HYPOTHESIS: As Mo play a significant role in the development of acute colitis, we hypothesized that receptor-mediated ErbB4 signaling may be an anti-inflammatory mechanism to limit Mo numbers during inflammation. METHODS: Mice (C57Bl6) were given 3% dextran sodium sulfate (DSS) in drinking water for 4 days (injury phase) followed by 3 days without DSS (recovery phase); colonic Mo populations were characterized by flow cytometry. Murine bone marrow-derived Mo (BM-Mo) were generated for in vitro activation and survival s...