IL-3 orchestrates ulcerative colitis pathogenesis by controlling the development and the recruitment of splenic reservoir neutrophils.
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| Abstract |
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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| Authors | 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 |
| Journal | Cell reports (Cell Rep) Vol. 42 Issue 6 Pg. 112637 (06 27 2023) ISSN: 2211-1247 [Electronic] United States |
| PMID | 37300834 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved. |
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