Cross-species transcriptomic signatures predict response to MK2 inhibition in mouse models of chronic inflammation

Summary: Inflammatory 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...

Description complète

Enregistré dans:
Détails bibliographiques
Auteurs principaux: Lucia Suarez-Lopez, Bing Shui, Douglas K. Brubaker, Marza Hill, Alexander Bergendorf, Paul S. Changelian, Aisha Laguna, Alina Starchenko, Douglas A. Lauffenburger, Kevin M. Haigis
Format: article
Langue:EN
Publié: Elsevier 2021
Sujets:
Q
Accès en ligne:https://doaj.org/article/76c5639d0d49434cae5abe91c97fbaf5
Tags: Ajouter un tag
Pas de tags, Soyez le premier à ajouter un tag!
Description
Résumé:Summary: Inflammatory 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.