Study of the role of IL-12p40-related cytokines in colitis of NEMOIEC-KO mice

Disruption of the epithelial barrier is considered a potential cause of inflammatory bowel disease (IBD). In this study, we employed the NEMOIEC-KO mouse model to study the immune mechanisms triggering chronic colitis downstream of an epithelial barrier defect. Colitis in NEMOIEC-KO mice is driven by commensal bacteria sensing through MyD88 signaling. The IL-12p40-related cytokines are induced upon microbial sensing and are known to act critically in promoting intestinal inflammation. Yet, the relative contribution of IL-12 versus IL-23 in eliciting intestinal pathology has been controversial. Using IL-12p40, IL-12p35 and IL-23p19 knockout mice we assessed the functional contribution of IL-12 and IL-23 to intestinal inflammation in the NEMOIEC-KO model. Overall design: To investigate how p40, p35 or p19 deficiencies affect the inflammatory response in the colon of NEMOIEC-KO mice, we conducted RNA-seq-based transcriptome profiling in the colons of 6-week-old NEMOIEC-KO Il12b-/-, NEMOIEC-KO Il12a-/-, NEMOIEC-KO Il23a-/-, NEMOIEC-KO and Nemofl/fl mice. Five mice per genotype were used as biological replicates.