Unravelling the pathogenesis of inflammatory bowel disease

Inflammatory bowel diseases (IBDs) — a broad classification that includes Crohn's disease and ulcerative colitis — are multigenic disorders that are also linked to various environmental components. Despite this complexity, considerable progress has been made in unravelling their pathogenesis. Ramnik Xavier and Daniel Podolsky review recent developments in the field. The genetics of IBDs point to roles for epithelial barrier function, innate and adaptive immunity in pathogenesis, while key environmental factors include commensal bacteria which may provoke dysregulated immune responses in the susceptible host. The advances made in understanding IBDs show what is possible in dissecting the pathogenesis of complex disorders: similar unbundling may be possible in heart disease, diabetes and other multigenic disorders. The cover shows an image of an activated human macrophage, one of several cell populations key to the pathogenesis of IBD.