| 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
|
| Resource |
| Mice |
RBRC02298 |
