Figure 7.

Illustration of key mediators involved in the development of acute intestinal GvHD (aGvHD) and IBD. aGvHD is caused by donor T cells responding to and attacking recipient host alloantigens with cytotoxic products. Irradiation and BMT conditioning prior to the BMT injure the intestinal epithelium, leading to intestinal barrier disruption and exposure of the mucosal immune compartment to bacterial products. These bacterial components are potent activators of an innate immune response, which trigger a “cytokine storm”, amplifying the immune response and favoring the development of acute GvHD. IBD, such as Crohn’s disease, develops due to the presence of a large inflammatory cell infiltrate with extensive mucosal and transmural injury including edema, loss of goblet cells, decreased mucous production and crypt cell hyperplasia. Factors secreted by the intestinal microbiota and immune cells can activate epithelial cells to produce cytokines that regulate inflammation, chemokines that signal recruitment of phagocytes, and growth factors with autocrine actions that facilitate epithelial repair and/or damage.