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

Autor:	Ullrich KA; Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Derdau J; Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Baltes C; Experimental Physics, Saarland University, Saarbrücken, Germany., Battistella A; Max Planck Institute for the Science of Light & Max-Planck-Zentrum für Physik und Medizin, Erlangen, Germany., Rosso G; Max Planck Institute for the Science of Light & Max-Planck-Zentrum für Physik und Medizin, Erlangen, Germany., Uderhardt S; Department of Medicine 3, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Exploratory Research Unit, FAU Optical Imaging Competence Center, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Erlangen, Germany., Schulze LL; Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Liu LJ; Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Dedden M; Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Spocinska M; Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Kainka L; Experimental Physics, Saarland University, Saarbrücken, Germany., Kubánková M; Max Planck Institute for the Science of Light & Max-Planck-Zentrum für Physik und Medizin, Erlangen, Germany., Müller TM; Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Erlangen, Germany., Schmidt NM; Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Becker E; Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Ben Brahim O; Department of Medicine 3, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Exploratory Research Unit, FAU Optical Imaging Competence Center, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Erlangen, Germany., Atreya I; Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Erlangen, Germany., Finotto S; Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Erlangen, Germany.; Department of Molecular Pneumology, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Prots I; Dental Clinic 1 - Dental Preservation and Periodontology, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Wirtz S; Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Erlangen, Germany., Weigmann B; Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Erlangen, Germany., López-Posadas R; Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Erlangen, Germany., Atreya R; Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Erlangen, Germany., Ekici AB; Institute of Human Genetics, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Lautenschläger F; Experimental Physics, Saarland University, Saarbrücken, Germany.; Center for Biophysics, Saarland University, Saarbrücken, Germany., Guck J; Max Planck Institute for the Science of Light & Max-Planck-Zentrum für Physik und Medizin, Erlangen, Germany., Neurath MF; Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany markus.neurath@uk-erlangen.de.; Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Erlangen, Germany., Zundler S; Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Erlangen, Germany.
Jazyk:	angličtina
Zdroj:	Gut [Gut] 2023 Nov; Vol. 72 (11), pp. 2081-2094. Date of Electronic Publication: 2023 Aug 04.
DOI:	10.1136/gutjnl-2023-329818
Abstrakt:	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. Competing Interests: Competing interests: MFN has served as an advisor for Pentax, Giuliani, MSD, AbbVie, Janssen, Takeda and Boehringer. SZ received honoraria from Takeda, Roche, Galapagos, Ferring, Falk, Lilly and Janssen. MFN and SZ received research support from Takeda, Shire (a part of Takeda) and Roche. JG and MK are co-founders of Rivercyte GmbH, a company that develops biomedical applications for real-time deformability cytometry. The other authors declare no conflicts of interest. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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