Inflammablog 5!

Review: Innate and Adaptive Immunity in Inflammatory Bowel Disease (IBD)

Inflammatory bowel diseases are the results of a dysregulated mucosal immune system. The mucosal immune system have both innate and adapative immunity. This review article presents the cross-regulation between these two immune systems and understanding the cross-regulation can help us to better understand the disease and possibly identify the future therapeutic targets.

IBD is idiopathic disease, but many soursces say that there is a genetic component for the cause. Genome-wide association studies (GWAS) provided a strong evidence for a close link between the innate and the adaptive immune system in regulating the sensitive balance of the mucosal immune system.

In the intestine, innate immunity includes the epithelial barrier and phagocytic cells within the lamina propria. The genetic defects in innate immunity can increase the incidence of IBD according to the paper.

For the adaptive immunity, Th1-mediated immune responses are typically evoked in response to an intracellular pathogen presented by antigen-presenting cell in the presence of IL-12. Then, the consequencial response is to localize the infectious agent and secret other cytokines like IFN-gamma and cytotoxic T cell for apoptosis. Th17 secret IL-12 and IL-22 which are pro-inflammatory and in inflamed Crohn's disease (CD) mucosa, there was an increasing level of IL-17 and IL-22. There are Treg cells which secrete IL-10, a potent anti-inflammatory cytokine and IL-10 deficient mice develop intestinal inflammation. Another form of IBD, Ulcerative Colitis (UC) had increasing levels of IL-13 and IFN-gamma which targets the epithelial cell to become dysfunctional. So, UC is more of superficial epithelial injury disorder.

Under which conditions does dysregulation of innate and adaptive immunity occur? Luminal antigens cross the epithelial barrier, and this process is increased during intestinal inflammation. The antigens reaching the lamina propria will first activate the innate immune system via pattern recognition receptors (PRRs) and antigen presenting cells (APCs) show antigens to T cell to evoke an adaptive immunity.

This article picked two examples to illlustrate the cross-regulation of innate and adaptive immunity. One example is NOD2, a cytoplasmic protein acting as PRR that serves as a bacteria sensor for the proteins on the cell wall of bacteria. Mice lacking NOD2 showed a defect in intestinal innate defense. CD patients with mutant NOD2 were shown to have decreased defensins and an increase of bacterial translocation and thus activating the adaptive immune system. The second example this article gives is IL-12. IL-12 is a key Th1 cytokine and CD is classified as a Th1-mediated disease. IL-12 is produced a lot by macrophages and dendritic cells within the lamina propria after the translocation of the bacteria and it will ultimately lead to the inflammation by Th1-mediated process. A mutation in NOD2 is associated with increase in IL-12, thus linking a receptor of the innate immunity with the effector cascade of the adaptive immunity. So, anti-IL-12 treatment is effective in patients with CD.

Source: Siegmund, Britta, and Martin Zeitz. "Innate and adaptive immunity in inflammatory bowel disease." World Journal of Gastroenterology. 17.27 (2011): 3178-3183.