Immunopathology of Inflammatory Bowel Disease and The Role of Toll-like Receptors Therein
Immunopathology of Inflammatory Bowel Disease and The Role of Toll-like Receptors Therein
Shahab Rabiee Lalehdashti,1,*Zahra Ahmadian Khortoumi,2Haniyeh Roudabadi Tanha,3
1. Department of Biology, Faculty of Science, Rasht branch Isamic Azad University, Gilan, Iran 2. Department of Biology, Faculty of Science, Rasht branch Islamic Azad University, Gilan, Iran 3. Department of Biology, Faculty of Science, Rasht branch Islamic Azad University, Gilan, Iran
Introduction: Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, which mainly includes Crohn's disease and ulcerative colitis. Ulcerative colitis is limited to the large intestine, which can lead to ulceration and bleeding; But Crohn's disease can affect any part of the digestive system and can lead to abscesses and abdominal pain. The pathophysiology of inflammatory bowel disease includes genetic, environmental, epithelial, microbial, and immunological factors. Several evidences suggest that IBD results from a dysregulation of the immune response to symbiotic organisms.
One of the main factors in the pathogenesis of IBD is immune system disorders. Different components of the mucosal immune system are involved in the pathogenesis of IBD. The clearest example is the intestinal immune system, which must establish the required balance between the immune response to symbiotic bacteria and pathogenic bacteria. Various studies have shown that epithelial barrier function, immune system, and regulation of immune response are known as key elements of intestinal homeostasis so disruption in these can lead to IBD.
Epithelial cells secrete Mucin and Defensin to protect themselves against the invasion of bacteria and other invading agents. Mucin is a glycoprotein that prevents bacteria from coming into contact with digestive cells by forming an adhesive physical barrier. In addition to mucin, an antimicrobial peptide called defensin is also secreted by digestive epithelial cells, which has a protective function against luminal bacteria, and a defect in their production allow pathogenic bacteria to invade epithelial cells and cause intestinal inflammation.
However according to a series of other studies, both innate and adaptive immune systems are involved in the occurrence of IBD.
Toll-like receptors (TLRs) are a family of pattern recognition receptors that are found on cell surfaces and intracellular membranes that as a member of innate immunity play an important role in identifying pathogens, maintaining intestinal homeostasis, controlling immune responses, and shaping the microbiota.
TLRs have been identified in both intestinal epithelial cells and gastrointestinal stromal tissue cells. Expression of TLR in the epithelium of the gastrointestinal tract varies from person to person. For example, the expression of TLR2, 4, 8, and 9 genes increases in patients with ulcerative colitis, while TLR5 is upregulated in active ulcerative colitis and downregulated in inactive ulcerative colitis. In fact, the activation of TLR signaling induces the stimulation of inflammatory cytokines which may be a precursor to the onset of inflammatory diseases such as IBD.
Further studies have also demonstrated that TLR4 can cause tissue destruction and ulceration in the intestine. TLR3 is significantly reduced in epithelial cells of patients with active IBD. Based on their research, a team of scientists identified TLR6 as the trigger for experimental colitis. Furthermore, based on other findings, TLR6 was introduced as a potential target for the treatment of IBD. As a result, each member of the TLR family and its subsets plays both positive and negative roles in the emergence of IBD.
Methods: Various experiments have been conducted by scientists to study the positive and negative roles of TLRs and their subsets in IBD.
Results: In various trials, TLRs and their activators have been found to have significant positive and negative effects on IBD. Interleukins and Interferons are known to be effective cytokines in TLR activity.
For instance, in one experiment, IFN-β was found to induce a positive clinical response and remission in a large number of patients with ulcerative colitis by modulating innate immune system function and regulate macrophage and dendritic cells function.
In a series of studies, TLR4 has been shown to have a dual role in IBD. As it can maintain the integrity of the intestinal lining and prevent the entry of harmful bacteria, it can also cause the destruction of tissues and wounds. It has been confirmed that stimulated intestinal glial cells can release and activate inflammatory cytokines by releasing nitric oxide, leading to exacerbation of intestinal inflammation.
Conclusion: More research is needed on IBD. Further research into the role of the immune system and the interaction of various immune components with the microbiota may open new horizons for further identification of IBD.