The role of the NF-ΚB2 pathway in inflammatory bowel disease

[摘要] Perturbed NF-κB activity has been indentified in vitro and in vivo, as a potential factor in IBD and there is a lack of knowledge with regards to the role played by the alternative NF-κB pathway in the events leading to IBD.Our experiments show that Nfκb2\(^-\)\(^/\)\(^-\) mice are resistant to acute, DSS induced colitis when compared to Wt mice placed on the same procedure. Characterization of cellular infiltrates in the mesenteric lymph nodes of the Nfκb2\(^-\)\(^/\)\(^-\) mice before and after the DSS procedure, showed a higher population of non-reactionary CD3\(^+\)CD4\(^+\)IL17\(^+\)FOXP3\(^+\) cells. Splenic studies revealed the Nfκb2\(^-\)\(^/\)\(^-\)mice display a reactionary B10 B cell population despite the mice suffering from a reduced total number of B cells. Nfκb2\(^-\)\(^/\)\(^-\) Rag1\(^-\)\(^/\)\(^-\) ,CD3ε\(^-\)\(^/\)\(^-\) and RelB\(^-\)\(^/\)\(^-\) mice placed on DSS treatment were found to be equally susceptible when compared to their Wt counterparts. Results from our chronic models of colitis showed no significant differences between Nfκb2\(^-\)\(^/\)\(^-\) mice and Wt littermate controls in terms of susceptibility to colitis. Our studies showed that crossing p100\(^-\)\(^/\)\(^-\) mice with LtβR\(^-\)\(^/\)\(^-\) mice partially rescues the LtβR\(^-\)\(^/\)\(^-\) phenotype. The cervical and mesenteric lymph nodes of these mice have identifiable expression of CXCL13, CCL21, Gp38 and CR1 as evidenced by immune-fluorescence microscopy.

[发布机构] University:University of Birmingham;Department:School of Immunity and Infection

[关键词] R Medicine;RC Internal medicine;RC0254 Neoplasms. Tumors. Oncology (including Cancer)