IL-3 orchestrates ulcerative colitis pathogenesis by controlling the development and the recruitment of splenic reservoir neutrophils

Autor: Alan Bénard, Anke Mittelstädt, Bettina Klösch, Karolina Glanz, Jan Müller, Janina Schoen, Björn Nüse, Maximilian Brunner, Elisabeth Naschberger, Michael Stürzl, Jochen Mattner, Luis E. Muñoz, Kai Sohn, Robert Grützmann, Georg F. Weber
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cell Reports, Vol 42, Iss 6, Pp 112637- (2023)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2023.112637
Popis: Summary: Inflammatory 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.
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