The Expression And Function Of Interleukin-23Receptor In Crohn’s Disease

As an infectious non-specific inflammatory granulormatous disease, Crohn’s disease (CD) has been reported to be related to the cellular immunity of Th17cells. And IL-23/IL-17signaling pathway plays a key role in the process of differentiation of Th17cells. But the expression and function of IL-23R is currently unclear.In our study, we would detected the IL-23R and IL-17A expression between the intestinal mucosa of CD and normal. And we also separated the human peripheral blood CD4+T cells by magnetic bead separation and induced them to differntiate to Th17cells by cytokines. By using the anti-human IL-23R monoclonal antibody, we would observe the function of IL-23R to the differntiation of Th17cells.Part I The Expression of Interleukin-23Receptor and Interleukin-17a in Patients with Crohn’s DiseaseObjective:To investigate the function and significance of interleukin-23receptor (IL-23R) and interleukin-17a (IL-17A) in the pathogenesis of Crohn’s disease (CD) by detecting the expression in the intestinal mucosal of patients with CD. Methods:Intestinal or colonic mucosal biopsies of32patients with Crohn’s disease (CD) and27healthy controls were chosen. The expression of IL-23R and IL-17A was detected by real-time PCR and the situ expression of IL-23R and IL-17A in intestinal mucosa was analyzed with immunohistoehemistry. Results:Compared with that in healthy controls, the expression of IL-23R at mRNA level in inflamed mucosa of CD patients increased significantly (P<0.05); The expression of IL-17A at mRNA level in inflamed mucosa of CD patients increased significantly (P<0.05). The immunohistochemistry results indicated that more IL-23R and IL-17A positive cells were in the intestinal or colonic mucosa of CD patients, and the expression of IL-23R and IL-17A in normal lamina mucosa was low. The expression of IL-23R and IL-17A protein in the intestinal or colonic mucosa of CD patients increased significantly (P<0.05). Conclusion:The expression of IL-23R and IL-17A in the intestinal mucosa of CD patients increased significantly, which suggested that abnormal IL-23R and IL-17A expression may had closely relation with the pathogenesis of CD. IL-23R and IL-17A may be a new target for the CD treatment.Part II The role of IL-23receptor antibody in the differentiation of CD4~+T cells in the p=eripheral bloodObjective:To investigate the expression of transcriptin factors in CD4+T cells in the peripheral blood after stimulation of anti-human IL-23R antibody. Methods:CD4+T cells in the peripheral blood, isolated by magnetic affinity cell sorting, were differatiated by TNF-βland IL-6, and also treated with anti-human IL-23R antibody to intervene their differentiation. The transcription factors in CD4+T cells were detected by Real-time PCR and Western-Blot. Results:With the differentiation of Th17cells, the expression of IL-23R, RORR-y and IL-17A were markedly increased. And with the treatment of IL-23R antibody, the expression of IL-23R, RORR-γ and IL-17A were decreased. Conclusion:It shows that IL-23R antibody could inhitor the differentiation of Th17cell. IL-23R antibody may be a new target for the CD treatment.