Inflammatory bowel disease and celiac disease: overlaps in the pathology and genetics, and their potential drug targets.
Inflammatory bowel disease, which covers Crohn's disease and ulcerative colitis, and celiac disease are both inflammatory diseases of the intestinal tract. In both diseases an antigen activates several inflammatory pathways, which cause extensive damage to the intestinal mucosa and lead to increased permeability of the intestinal epithelium. The causative antigen in inflammatory bowel disease is the microflora in the intestinal lumen, facilitated by an impaired innate immune system that is unable to halt the invasion of microbes into the lamina propria. These provoke T helper 1 and T helper 17 responses in Crohn's disease and a T helper 2 response in ulcerative colitis. Pro-inflammatory cytokines and interleukins produced in these processes lead to impairment of tight junctions and increased permeability of the intestinal epithelial lining. In celiac disease, inflammation is caused by dietary gluten, a peptide present in wheat, barley and rye. In genetically predisposed people, gliadin peptides (derivatives of gluten) are presented on the Human Leukocyte Antigen DQ2 or DQ-8 molecules of antigen-presenting cells to T helper cells. This provokes a T helper 1 response, which leads to the production of pro-inflammatory cytokines and subsequent damage to, and increased permeability of the intestinal epithelium. We describe the details and overlaps in the pathomechanism and genetics of inflammatory bowel disease and celiac disease, and discuss potential drug targets for intervention.
Festen
Eleonora A M
EA
Department of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
Szperl
Agata M
AM
Weersma
Rinse K
RK
Wijmenga
Cisca
C
Wapenaar
Martin C
MC
D002446:Celiac Disease / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D020381:Interleukin-17 / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000502:physiology; D010539:Permeability; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D020381:Interleukin-17; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein