IL-3 receptor signalling suppresses chronic intestinal inflammation by controlling mechanobiology and tissue egress of regulatory T cells.

Ullrich K, Derdau J, Baltes C, Battistella A, Rosso G, Uderhardt S, Schulze L, Liu L, Dedden M, Spocinska M, Kainka L, Kubánková M, Müller T, Schmidt NM, Becker E, Ben Brahim O, Atreya I, Neurath-Finotto S, Prots I, Wirtz S, Weigmann B, Lopez Posadas R, Atreya R, Ekici AB, Lautenschläger F, Guck J, Neurath M, Zundler S (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Gut BMJ Publishing Group

Book Volume: 72

Pages Range: 2081-2094

Journal Issue: 11

DOI: 10.1136/gutjnl-2023-329818

Abstract

IL-3 has been reported to be involved in various inflammatory disorders, but its role in inflammatory bowel disease (IBD) has not been addressed so far. Here, we determined IL-3 expression in samples from patients with IBD and studied the impact of Il3 or Il3r deficiency on T cell-dependent experimental colitis. We explored the mechanical, cytoskeletal and migratory properties of Il3r -/- and Il3r +/+ T cells using real-time deformability cytometry, atomic force microscopy, scanning electron microscopy, fluorescence recovery after photobleaching and in vitro and in vivo cell trafficking assays. We observed that, in patients with IBD, the levels of IL-3 in the inflamed mucosa were increased. In vivo, experimental chronic colitis on T cell transfer was exacerbated in the absence of Il-3 or Il-3r signalling. This was attributable to Il-3r signalling-induced changes in kinase phosphorylation and actin cytoskeleton structure, resulting in increased mechanical deformability and enhanced egress of Tregs from the inflamed colon mucosa. Similarly, IL-3 controlled mechanobiology in human Tregs and was associated with increased mucosal Treg abundance in patients with IBD. Collectively, our data reveal that IL-3 signaling exerts an important regulatory role at the interface of biophysical and migratory T cell features in intestinal inflammation and suggest that this might be an interesting target for future intervention.

Authors with CRIS profile

Karen Ullrich Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Stefan Uderhardt Department of Medicine 3 – Rheumatology and Immunology Lisa Schulze Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Lijuan Liu Lehrstuhl für Innere Medizin I (Medizin 1) Mark Dedden Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Tanja Müller Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Emily Becker Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Imke Atreya Medizinische Fakultät Susetta Neurath-Finotto Professur für Molekulare Pneumologie Iryna Prots Department of Operative Dentistry and Periodontology Stefan Wirtz Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Benno Weigmann Medizinische Fakultät Rocío Lopez Posadas Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Raja Atreya Professur für Translationale Immunforschung bei chronisch entzündlichen Darmerkrankungen Arif Bülent Ekici Institute of Human Genetics Jochen Guck
Markus Neurath Lehrstuhl für Innere Medizin I (Medizin 1) Sebastian Zundler Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung (IZKF)

Related research project(s)

A104: Mechanical regulation of intestinal T cell egress in inflammatory bowel disease June 1, 2023 - Nov. 30, 2025

Involved external institutions

Max-Planck-Institut für die Physik des Lichts (MPL) / Max Planck Institute for the Science of Light DE Germany (DE) Universität des Saarlandes (UdS) DE Germany (DE)

How to cite

APA:

Ullrich, K., Derdau, J., Baltes, C., Battistella, A., Rosso, G., Uderhardt, S.,... Zundler, S. (2023). IL-3 receptor signalling suppresses chronic intestinal inflammation by controlling mechanobiology and tissue egress of regulatory T cells. Gut, 72(11), 2081-2094. https://doi.org/10.1136/gutjnl-2023-329818

MLA:

Ullrich, Karen, et al. "IL-3 receptor signalling suppresses chronic intestinal inflammation by controlling mechanobiology and tissue egress of regulatory T cells." Gut 72.11 (2023): 2081-2094.

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