RRC ID 75814
Author Bénard A, Mittelstädt A, Klösch B, Glanz K, Müller J, Schoen J, Nüse B, Brunner M, Naschberger E, Stürzl M, Mattner J, Muñoz LE, Sohn K, Grützmann R, Weber GF.
Title IL-3 orchestrates ulcerative colitis pathogenesis by controlling the development and the recruitment of splenic reservoir neutrophils.
Journal Cell Rep
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.
Volume 42(6)
Pages 112637
Published 2023-6-8
DOI 10.1016/j.celrep.2023.112637
PII S2211-1247(23)00648-4
PMID 37300834
IF 8.109
Mice RBRC02298