Cross-species comparative transcriptomics examining the role of Type-2 immunity in acute colitis

Most preclinical models of IBD were developed in mice which share 85% genomic homology with humans and are genetically tractable. However, rats have historically been the model of choice for immunologic, cardiovascular, and neurologic diseases because they more closely recapitulate human physiology6. Recent work on the role of microbial dysbiosis in IBD has also shown that rat microbiota is more closely related to those of humans than mice7. Taken together, this suggests that a single preclinical model may not be optimal for delineating the molecular pathways involved in IBD pathogenesis. Previous research in rat models of IBD have focused primarily on characterization of clinical score and histopathological findings8, with a lack of systematic investigation into potential molecular pathways affected, thereby making it difficult to integrate this model with other preclinical and clinical research. In the current study, we have undertaken a systematic transcriptomic analysis of a rat model of experimental colitis along with a three-way comparison between an established mouse preclinical model and available human clinical datasets in an effort to identify conserved immunological pathways in IBD. Overall design: IBD was induced using chemical DSS at a concentration of 5.5 % w/v in drinking water for rats for 6 days. At the end of day 6 rats were sacrified and whole colonic tissue was collected and homogenized in trizol (Thermofisher Scientific, USA). RNA extraction was then done using RNA mini kit (Qiagen, Germany) according to the manufacturer's guidelines with the quality of RNA evaluated using an Agilent bioanlyzer 2100 system. Samples with RNA integrity number (RIN) = 6.8 were considered for library preparation. IL: distal ileum RC: Right (proximal) colon LC: Left (distal) colon