ד"ר מקסים סקסונוב - Clcn5 Knockout Mice Exhibit Novel Immunomodulatory Effects and Are More Susceptible to Dextran Sulfate Sodium-Induced Colitis

he inflammatory bowel disease (IBD) can be manifested in the affected individuals in the formofCrohn’s disease (CD) and ulcerative colitis (UC), the disease profiles of which are not clearly defined in terms of their etiology and pathogenesis. Various reports have linked mucosal immune system of gut lining with intestinal inflammation and chemicals like cytokines which are inflammatory mediators, play a crucial role in modulating this immune system. The expression of some proteins like chlorine exchanger, Clc-5, was found to be decreased in active ulcerative colitis (UC) and hence its role in mucosal immune response was investigated. Acute colitis was mimicked by giving dextran sulfate sodium (DSS) to normal mice and to mice in which Clcn5 gene was deleted. The two experimental groups showed significant differences in disease activity. The levels of various cytokines like TNF-a, IL-6, and IL-17 were increased in the serum of DSS-treated Clcn5 mice compared with that in normal mice confirming inflammation. A treatment with vitamin D reversed these outcomes in DSS-treated Clcn5 mice, which suggested the protective potential of diet in the diseased individuals. Since ulcerative colitis is modulated by both genetic and environmental factors, this finding suggested that in patients with abnormal CLC5, diet would be able to impact the severity of symptoms. The protein expression of many molecules was checked by imaging and western blot analysis and the protein involved in an inflammatory pathway known as NF-kB pathway, were found to be activated in the DSS-treated Clcn5 mice. These results studied and defined the role of CLC-5 in the disease progression of ulcerative colitis to provide a better understanding of the ulcerative colitis-associated diarrhea. This research can thus provide new effective individually tailored strategies to generate novel and efficient therapeutic targets for the management of diarrhea and other symptoms in ulcerative colitis patients. Since many ion transporter proteins have been linked with cancer, it would be interesting to see if Clcn5 also plays some role in its progression.