Revisiting Crohn's disease as a primary immunodeficiency of macrophages

Despite two decades of mouse immunology and human genetics studies, the pathogenesis of Crohn's disease (CD) remains elusive. New clinical investigations suggest that CD may be caused by inborn errors of macrophages. These errors may result in impaired attraction of granulocytes to the gut wall, causing impaired clearance of intruding bacteria, thereby precipitating the formation of granulomas. This theory paves the way for a macrophage-based Mendelian genetic dissection of CD.