Type I interferons have opposing effects during the emergence and recovery phases of colitis
- Autor(en)
- Isabella Rauch, Eva Hainzl, Felix Rosebrock, Susanne Heider, Clarissa Schwab, David Berry, Dagmar Stoiber, Michael Wagner, Christa Schleper, Alexander Loy, Tim Urich, Mathias Müller, Birgit Strobl, Lukas Kenner, Thomas Decker
- Abstrakt
The contribution of the innate immune system to inflammatory bowel disease (IBD) is under intensive investigation. Research in animal models has demonstrated that type I interferons (IFN-Is) protect from IBD. In contrast, studies of patients with IBD have produced conflicting results concerning the therapeutic potential of IFN-Is. Here, we present data suggesting that IFN-Is play dual roles as regulators of intestinal inflammation in dextran sodium sulfate (DSS)-treated C57BL/6 mice. Though IFN-Is reduced acute intestinal damage and the abundance of colitis-associated intestinal bacteria caused by treatment with a high dose of DSS, they also inhibited the resolution of inflammation after DSS treatment. IFN-Is played an anti-inflammatory role by suppressing the release of IL-1β from the colon MHC class II+ cells. Consistently, IL-1 receptor blockade reduced the severity of inflammation in IFN-I receptor-deficient mice and myeloid cell-restricted ablation of the IFN-I receptor was detrimental. The proinflammatory role of IFN-Is during recovery from DSS treatment was caused by IFN-I-dependent cell apoptosis as well as an increase in chemokine production and infiltrating inflammatory monocytes and neutrophils. Thus, IFN-Is play opposing roles in specific phases of intestinal injury and inflammation, which may be important for guiding treatment strategies in patients.
- Organisation(en)
- Department für Mikrobiologie, Immunbiologie und Genetik
- Externe Organisation(en)
- Medizinische Universität Wien, Veterinärmedizinische Universität Wien, Ludwig Boltzmann Institut für Krebsforschung
- Journal
- European Journal of Immunology
- Band
- 44
- Seiten
- 2749-2760
- Anzahl der Seiten
- 12
- ISSN
- 0014-2980
- DOI
- https://doi.org/10.1002/eji.201344401
- Publikationsdatum
- 08-2014
- Peer-reviewed
- Ja
- ÖFOS 2012
- 106022 Mikrobiologie, 106023 Molekularbiologie, 301902 Immunologie
- Schlagwörter
- ASJC Scopus Sachgebiete
- Immunology, Immunology and Allergy
- Link zum Portal
- https://ucris.univie.ac.at/portal/de/publications/type-i-interferons-have-opposing-effects-during-the-emergence-and-recovery-phases-of-colitis(e4e85b67-01a1-4985-b926-d9ece082707f).html