title: Inflammation in the intestinal tract: pathogenesis and treatment.
abstract: Over the past decade a major hypothesis has emerged for the etiopathogenesis of inflammatory bowel disease (IBD). This hypothesis proposes that IBD represents a dysregulated mucosal immune response to antigens derived from the commensal microbiota in a genetically susceptible host that initially derives from innate immune abnormalities leading to an excessive proinflammatory cytokine derived from CD4+ T cells (T-helper 1, T-helper 2, and T-helper 17 cytokines) over and above the response that is normally associated with tolerance and immunoregulation derived from T-regulatory cells. Given that the genetic predisposition has increasingly been recognized to affect the regulation of innate and adaptive immunity, intestinal epithelial cell physiologic barrier function and the potential inappropriate access of antigens to the mucosal immune system through this dysfunctional barrier function, a key point in understanding IBD pathophysiology is to understand the immunoregulatory pathways associated with the intestinal immune system as they apply to IBD. Therefore, immunogenetic pathways associated with innate and adaptive immunity, the cytokines secreted by innate and adaptive immune cells, the epithelial factors and leukocyte factors that are associated with inflammation and structures on the endothelium that regulate the recruitment of leukocytes define potential pathways that may be amenable to therapeutic manipulation in IBD.
authors.affiliation: Gastroenterology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. 02115, USA. rblumberg@partners.org
authors.forename: Richard S
authors.initials: RS
authors.lastname: Blumberg
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D015212:Inflammatory Bowel Diseases / Q000209:etiology* / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D007413:Intestinal Mucosa / Q000473:pathology; D054892:Metagenome / Q000502:physiology
chemical_list: D016207:Cytokines