New insight into the role of the immune system in maintaining homeostasis of bacteria in the intestinal tract may be useful in the development of targeted therapies for various inflammatory bowel diseases, as well as colorectal cancer. The study, appearing online last week in Cell Reports identified a molecule, called Absent in Melanoma 2 (AIM2) that detects the DNA of harmful microorganisms and regulated inflammation in the gut. AIM2 is found in all immune and epithelial cells, and defects in AIM2 may adversely affect DNA sensing, thereby contributing to intestinal inflammatory disorders including IBD, ulcerative colitis, Crohn’s disease, and colorectal cancer.
The research found that when AIM2 detects the DNA of harmful microorganisms (pathogens) in immune and epithelial cells, the protein activates a molecular machine called the inflammasome. This in turn activates the enzyme caspase-1, which then produces 2 proteins (IL-1β and IL-18) that play important roles in the GI tract, including activation of immune cells, induction of antimicrobial peptides, and regulation of epithelial cell proliferation. But defects in AIM2-mediated inflammasome activation lead to growth of IBD-causing bacteria like E. coli, as well as dysregulated inflammation and compromised healing of intestinal injury. Senior author Hasan Zaki, PhD, Assistant Professor of Pathology at UT Southwestern Medical Center, commented on the findings, “By extension, manipulation of the AIM2 signaling pathway may be a promising treatment option for these conditions.”
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Read more about the research findings here.
The article abstract may be read here.