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Inflammatory Bowel Disease - Coggle Diagram
Inflammatory Bowel Disease
Compromised of two major disorders
Ulcerative colitis
Ulcerative colitis is a chronic inflammatory condition characterized by relapsing and remitting episodes of inflammation limited to the mucosal layer of the colon
Crohn's disease
Crohn disease is characterized by transmural inflammation and by skip lesions. The transmural inflammatory nature of Crohn disease may lead to fibrosis and strictures, and to obstructive clinical presentations that are not typically seen in ulcerative colitis. More commonly, the transmural inflammation results in sinus tracts, giving rise to microperforations and fistulae
May involve the entire gastrointestinal tract from mouth to perianal area. The most commonly affected area is the ileum and proximal colon
Mucosal immune system
Mutations in the IL-23 receptor have been associated with susceptibility to inflammatory bowel disease (IBD)
Targeting of both the p19 subunit (unique to IL-23) and the p40 subunit (common to both IL-12 and IL-23) has demonstrated efficacy in clinical trials for treatment of IBD
T cell plasticity has implications to therapy options
Inflammatory bowel disease
Dysregulated response by the mucosal immune system to the microbiota that reside within the intestinal lumen
Dysregulation of epithelial cells that are present within the gut
Excessive immune cell recruitment and activation has been detected in multiple immune cell subsets
Myeloid cells with an "inflammatory" phenotype that produce increased levels of cytokines are present in the lamina propria
Natural killer (NK) cells subsets are altered
T cells isolated from IBD mucosa may show increased proliferation and cytokine production to antigens in vitro, suggesting that they may respond abnormally to resident antigens
Circulating B cells and plasma cells, autoantibodies, and increased antibodies to microbial components in patients with IBD
Neutrophils, found within diseased mucosa in IBD are not usually present in the lamina propria and therefore must be recruited from the blood vessels.
Cytokines that are produced in the gut call for homing and enable adhesion to the blood vessels to be able to enter the gut tissue
Therapeutic strategies to block mucosal homing of leukocytes
Crohn's disease
CD4+ T lymphocytes isolated from patients with Crohn disease secrete large amounts of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, cytokines with a marked proinflammatory effect, thereby implicating Th1 cells in the pathogenesis of IBD
The secretion of interleukin (IL)-4, IL-5, and IL-13 by Th2 cells suppresses Th1-mediated responses, but also leads to the infiltration of eosinophils and can contribute to intestinal inflammation
The TL1A (TNFSF15)/DR3 axis has also been implicated in Crohn disease. TL1A is a TNF-like cytokine that is increased in Crohn disease and interacts with the death domain receptor (DR3).
Several studies have implicated the TL1A/DR3 axis in animal models of colitis, with studies suggesting that TL1A can lead to induction of cytokines from Th1, Th2, and Th17 cells; NK cells; myeloid cells; and innate lymphoid cells