Volume 151, Issue 4, Pages 593-596 (October 2016) Granulocyte-Macrophage Colony Stimulating Factor Bioactivity and Mucosal Homeostasis in Crohn’s Disease: A Role for Genetic Variation  Lee A. Denson  Gastroenterology  Volume 151, Issue 4, Pages 593-596 (October 2016) DOI: 10.1053/j.gastro.2016.08.042 Copyright © 2016 AGA Institute Terms and Conditions

Figure 1 Genetic and acquired variation in granulocyte-macrophage colony stimulating factor (GM-CSF) bioactivity regulates monocyte dependent mucosal homeostasis in Crohn’s disease. GM-CSF–dependent STAT5 tyrosine phosphorylation in monocytes and macrophages is a predominant signaling mechanism in the human gut. Under normal conditions, GM-CSF priming enhances both antimicrobial and immunoregulatory properties of intestinal monocytes and macrophages. GM-CSF bioactivity may be reduced by common acquired mechanisms including neutralizing GM-CSF autoantibodies or reduced transcription of the GM-CSF receptor alpha chain gene. In the current report, a rare frameshift mutation in the GM-CSF receptor beta chain gene is also shown to reduce GM-CSF dependent STAT5 activation, and increase risk for Crohn’s disease. Collectively, these acquired and genetic reductions in cellular GM-CSF signaling disrupt mucosal homeostasis and contribute to chronic gut inflammation. IL, interleukin; TLR4, Toll-like receptor 4; TNF, tumor necrosis factor. Gastroenterology 2016 151, 593-596DOI: (10.1053/j.gastro.2016.08.042) Copyright © 2016 AGA Institute Terms and Conditions