摘要：SummaryInflammatory bowel diseases (IBDs) are genetically complex and exhibit significant inter-patient heterogeneity in disease presentation and therapeutic response. Here, we show that mouse models of IBD exhibit variable responses to inhibition of MK2, a pro-inflammatory serine/threonine kinase, and that MK2 inhibition suppresses inflammation by targeting inflammatory monocytes and neutrophils in murine models. Using a computational approach (TransComp-R) that allows for cross-species comparison of transcriptomic features, we identified an IBD patient subgroup that is predicted to respond to MK2 inhibition, and an independent preclinical model of chronic intestinal inflammation predicted to be non-responsive, which we validated experimentally. Thus, cross-species mouse-human translation approaches can help to identify patient subpopulations in which to deploy new therapies.Graphical abstractDisplay OmittedHighlights•MK2 kinase inhibition shows variable efficacy in different IBD mouse models•TCT and TNFΔARE mice express distinct inflammatory and MK2-responsive genes•“Response to MK2i” signature is enriched in monocytes and neutrophils•Cross-species modeling identifies patient groups potentially responsive to MK2iImmunology; Computational bioinformatics; Systems biology; Transcriptomics
