INFLAMMATORY BOWEL DISEASE: A BREAKDOWN IN IMMUNE SYSTEM COMMUNICATIONS

Inflammatory Bowel Disease (IBD) encompasses two distinct disorders, ulcerative colitis (UC) and Crohn's disease (CD). IBD is not to be confounded with irritable bowel syndrome (IBS), another intestinal disorder linked to inflammation, yet of distinct etiology and lower severity than IBS. The last decade has seen a profound change in the way scientists view the pathological process at play in IBD. Indeed, adaptive immune leukocytes (T and B cells) have been downgraded from the status of primary culprits in IBD, to that of secondary contributors, with leukocytes of the innate immune system now dominating the pathological picture at early and chronic stages of the disease.

The two forms of IBD, UC and CD, are both characterized by an aberrant function of resident macrophages and mast cells. These innate subsets are normally present in the intestinal mucosa, serving to limit aggressive innate immune responses to a minimum, in the context of a tissue laden with overwhelming amounts of bacteria. Both UC and CD are believed to stem from a breach in the default tolerance mode between the innate immune system and bacteria, with macrophages and mast cells increasing in number and displaying activated, inflammatory phenotypes and bacteria occasionally found to cross the epithelial lining into the mucosa.

The similarity between UC and CD stops there, however. On the one hand, UC features increased neutrophil and eosinophil recruitment and activation in the intestinal mucosa, reflecting a typical pro-inflammatory disease process. On the other hand, CD is characterized by a relative lack of neutrophils and the formation of macrophage-rich granulomas, typically seen in conditions of decreased neutrophil function. Thus, UC and CD seem to feature opposite types of neutrophil dysfunction. Scientists at Celtaxsys are pursuing novel therapeutic strategies aiming to modulate neutrophil, macrophage, and possibly mast cell migration and function in the intestinal mucosa, which could potentially lead to disease-changing outcomes in IBD.

Please visit the Crohn’s & Colitis Foundation of America to learn more about Crohn’s Disease and Ulcerative Colitis.