NRG4-ErbB4 signaling represses proinflammatory macrophage activity

Proinflammatory macrophages are essential drivers of colitis and express the growth factor receptor ErbB4. This study tested the role of ErbB4 and its specific ligand, NRG4, in regulating macrophage function. We show that endogenous NRG4-ErbB4 signaling limits macrophage production of proinflammator...

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Veröffentlicht in:	American journal of physiology: Gastrointestinal and liver physiology 2021-06, Vol.320 (6), p.G990-G1001
Hauptverfasser:	Schumacher, Michael A, Dennis, Isabella C, Liu, Cambrian Y, Robinson, Cache, Shang, Judie, Bernard, Jessica K, Washington, M Kay, Polk, D Brent, Frey, Mark R
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Apoptosis Bone marrow Cell activation Chronic illnesses Colitis Colitis - metabolism Colon - metabolism Cytokines Cytokines - metabolism ErbB-2 protein Feedback Growth factors Homeostasis Inflammation - genetics Inflammation - metabolism Inflammatory bowel disease Inflammatory bowel diseases Interleukin 1 Interleukin-10 - genetics Interleukin-10 - metabolism Ligands Lipopolysaccharides Macrophage Activation - physiology Macrophages Macrophages - metabolism Mice Mice, Knockout Neuregulins - metabolism Protein-tyrosine kinase receptors Receptor, ErbB-4 - metabolism Signal Transduction - physiology Tumor necrosis factor γ-Interferon
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Beschreibung
Zusammenfassung:	Proinflammatory macrophages are essential drivers of colitis and express the growth factor receptor ErbB4. This study tested the role of ErbB4 and its specific ligand, NRG4, in regulating macrophage function. We show that endogenous NRG4-ErbB4 signaling limits macrophage production of proinflammatory cytokines in vitro and limits colitis severity in vivo and thus is a potential target for therapeutic intervention.
ISSN:	0193-1857 1522-1547
DOI:	10.1152/ajpgi.00296.2020