Bénard, AlanAlanBénardMittelstädt, AnkeAnkeMittelstädtKlösch, BettinaBettinaKlöschGlanz, KarolinaKarolinaGlanzMüller, JanJanMüllerSchoen, JaninaJaninaSchoenNüse, BjörnBjörnNüseBrunner, MaximilianMaximilianBrunnerNaschberger, ElisabethElisabethNaschbergerStürzl, MichaelMichaelStürzlMattner, JochenJochenMattnerMuñoz, L. E.L. E.MuñozSohn, KaiKaiSohnGrützmann, RobertRobertGrützmannWeber, Georg FerdinandGeorg FerdinandWeber2023-10-022023-10-022023https://publica.fraunhofer.de/handle/publica/45118410.1016/j.celrep.2023.1126372-s2.0-85161594454Inflammatory bowel diseases (IBDs) are a global health issue with an increasing incidence. Although the pathogenesis of IBDs has been investigated intensively, the etiology of IBDs remains enigmatic. Here, we report that interleukin-3 (Il-3)-deficient mice are more susceptible and exhibit increased intestinal inflammation during the early stage of experimental colitis. IL-3 is locally expressed in the colon by cells harboring a mesenchymal stem cell phenotype and protects by promoting the early recruitment of splenic neutrophils with high microbicidal capability into the colon. Mechanistically, IL-3-dependent neutrophil recruitment involves CCL5+ PD-1high LAG-3high T cells, STAT5, and CCL20 and is sustained by extramedullary splenic hematopoiesis. During acute colitis, Il-3−/− show, however, increased resistance to the disease as well as reduced intestinal inflammation. Altogether, this study deepens our understanding of IBD pathogenesis, identifies IL-3 as an orchestrator of intestinal inflammation, and reveals the spleen as an emergency reservoir for neutrophils during colonic inflammation.enCCL5colitisCP: Immunologyinterleukin-3neutrophilsspleenjournal article