Role of reactive oxygen species on the intestinal macrophages development

Chronic granulomatous disease (CGD) is an immunodeficiency disease caused by defects in any one of the five structural components of the NADPH oxidase enzyme, i.e. X-linked reces-sive mutations in CYBB (gp91phox), or autosomal recessive mutations in CYBA (p22phox), NCF1 (p47phox), NCF2 (p67phox), NCF4 (p40phox). CGD results from reduced or absent reactive oxygen species (ROS) production. ROS play a crucial role in phagocytes; therefore, CGD patients are less capable to kill pathogens. I addition, and at the heart of this project proposal, around 50 % of patients with CGD suffer from severe intestinal inflammation which shares features with inflammatory bowel disease, according to a report of the National Institutes of Health. However, the molecular and cellular mechanisms underlying CGD colitis are largely unknown. Our hypotheses is that CGD is associated colitis involves dysregulation of resident intestinal macrophages. Sorted the lamina propria macrophages (Ly6Clow MHC-II+) from 6 weeks old WT, p47phox-/-, and gp91phox-/- mice.