The Exploration Of Function And Mechanism Of Susceptible Gene IFNα-4 Among Chinese Crohn’s Disease Patients In The Animal Model

Background and Aims:Crohn’s disease(CD)as one of the inflammatory bowel diseases,which is mainly caused by the imbalance of innate immunity and adaptive immune response of intestinal mucosa under the interaction of genetic,environmental and microecological factors.At present,more than 200 susceptible gene loci have been found in foreign studies.It has not been reported that the interaction of IFNα-4,a CD susceptibility gene,with intestinal specific microorganisms is involved in its pathogenesis.Therefore,in order to study the mechanism and function of IFN α-4 in CD genesis and development,we intend to study the pathogenesis of enteritis under the specific microbial interaction mediated by IFNα-4 and its mutant.Methods and results:Based on the constructed IFNα-4,IFNα-4-mut conditional transgenic mice,WT group,IFNα-4 group,IFNα-4-mutation group were set up,and DSS enteritis model was constructed.The diarrhea,weight,fecal blood and mental state of mice in different groups were observed,and the feces of mice were collected at different time points for 16S,its and virus macrogenomic sequencing,the collected feces of mice were cultured to find the characteristic strains related to IFNα-4 and IFN α-4-mut phenotype.Early experiments showed that the weight of IFNα-4 group transgenic mice in DSS induced acute enteritis model was restored quickly,the intestinal inflammation score was significantly reduced,while the weight of IFNα-4-mut group was significantly reduced and the intestinal inflammation score was deteriorated;sequencing experiments confirmed that at the same time,the mice in each model group had significantly different viruses,fungi and bacteria,in the IFNα-4-mut group,the number of Cellulophaga-phage-phi 19:1 and Synechococcus-phage-syn9 virus increased significantly,the abundance of Aspergillus-piperis decreased significantly,and the un-f-christensenellaceae also increased significantly.Conclusion:Our team has reported that heterozygote IFNα-4,10 mutations are CD susceptible genes and induce IFNα subtype functional defects.The results of ourprevious study suggest that IFNα-4 mutations may promote the occurrence of enteritis,and IFNα-4 has a protective effect on intestinal inflammation,and intestinal specific microorganisms also play an important role in the occurrence and development of enteritis,which is specific to intestinal tract microbial intervention may be a new effective treatment for inflammatory bowel disease.