母体炎性暴露对子代小鼠受IRBP抗原诱导的葡萄膜炎的影响OA北大核心CSTPCD

Objective To investigate the effect of embryonic inflammatory exposure on the response of mouse offspring to interphotoreceptor retinoid-binding protein(IRBP)-induced experimental autoimmune uveitis(EAU).Methods RNA transcriptome sequencing data from eyeballs of C57BL/6J mouse offspring born to mothers with active EAU were used to screen immune-associated differentially expressed genes in the eyes of the exposed offspring.Gene fragments overlapping in the two datasets were screened using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses to identify biological pathways associated with the gene fragments.Hub genes were identified from these intersecting genes by protein-protein interaction network analysis.EAU models of maternal uveitis were established by immunization with IRBP651-670,and expression levels of the pivotal genes in the offspring exposed to inflammation by maternal uveitis were examined by fluorescence quantitative polymerase chain reaction.EAU severity,T lymphocyte proliferation,and serum cytokines were detected to investigate the immune effect in offspring from mothers with an active inflammation response to IRBP induction.Results Microarray analysis identified 72 immune-related differentially expressed genes in exposed samples compared with the findings in control samples.These genes were mainly enriched in Toll-like receptor signaling,mitogen-activated protein kinase signaling,and B cell receptor signaling pathways.Protein-protein interaction network interaction analysis screened out four hub genes,Psmc5,Psmc3,Psmd4,and Psmd8,and mRNA levels of these four genes were increased in the adult offspring from mothers with active uveitis compared with the findings in healthy offspring.In addition,the group induced with 150 μg IRBP showed an increase in the severity of clinical and pathological outcomes in offspring with EAU affected by active inflammation,compared with the healthy offspring group(P=0.0087,P=0.0410).Meanwhile,T cell proliferation in the offspring was enhanced during the inflammatory activity stage and secretion of the inflammatory cytokines interleukin(IL)-17 and IL-6 was increased(P=0.0450,P=0.0300).Conclusions Psmc5,Psmc3,Psmd4,and Psmd8 may be important genes exacerbating uveitis in offspring of mothers with active uveitis,associated with increased T cell proliferation and production of IL-17 and IL-6.