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

Benard A, Mittelstädt A, Klösch B, Glanz K, Müller J, Schoen J, Nüse B, Brunner M, Naschberger E, Stürzl M, Mattner J, Munoz LE, Sohn K, Grützmann R, Weber G (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 42

Article Number: 112637

Journal Issue: 6

DOI: 10.1016/j.celrep.2023.112637

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-1^high LAG-3^high 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.

Authors with CRIS profile

Alan Benard Department of Surgery Anke Mittelstädt Department of Surgery Janina Schoen Department of Medicine 3 – Rheumatology and Immunology Maximilian Brunner Lehrstuhl für Allgemein- und Viszeralchirurgie Elisabeth Naschberger Department of Surgery Michael Stürzl Professur für Molekulare und Experimentelle Chirurgie Jochen Mattner Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Luis Munoz Becerra Department of Medicine 3 – Rheumatology and Immunology Robert Grützmann Lehrstuhl für Allgemein- und Viszeralchirurgie Georg Weber Department of Surgery

Additional Organisation(s)

FAU Profilzentrum Licht.Materie.Quantentechnologien (FAU LMQ)

Involved external institutions

Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB / Fraunhofer Institute for Interfacial Engineering and Biotechnology

Germany (DE)

How to cite

APA:

Benard, A., Mittelstädt, A., Klösch, B., Glanz, K., Müller, J., Schoen, J.,... Weber, G. (2023). IL-3 orchestrates ulcerative colitis pathogenesis by controlling the development and the recruitment of splenic reservoir neutrophils. Cell Reports, 42(6). https://doi.org/10.1016/j.celrep.2023.112637

MLA:

Benard, Alan, et al. "IL-3 orchestrates ulcerative colitis pathogenesis by controlling the development and the recruitment of splenic reservoir neutrophils." Cell Reports 42.6 (2023).

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