Type I interferons have opposing effects during the emergence and recovery phases of colitis

Autoren:Rauch, Isabella; Hainzl, Eva (Veterinärmedizinische Universität Wien); Rosebrock, Felix; Heider, Susanne (Medizinische Universität Wien); Schwab, Clarissa; Berry, David; Stoiber, Dagmar (Ludwig Boltzmann Institut für Krebsforschung); Wagner, Michael; Schleper, Christa; Loy, Alexander; Urich, Tim; Müller, Mathias (Veterinärmedizinische Universität Wien); Strobl, Birgit (Veterinärmedizinische Universität Wien); Kenner, Lukas (Medizinische Universität Wien); Decker, Thomas
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.

Sprache:Englisch
Anzahl der Seiten:12
Publikationsdatum:1.9.2014
Journaltitel:European Journal of Immunology
Volume:44
Nummer:9
Seiten:2749-2760
Peer reviewed:true
Links:
Digital Object Identifier (DOI):http://dx.doi.org/10.1002/eji.201344401
Publikationstyp:Artikel
Portal:https://ucris.univie.ac.at/portal/en/publications/type-i-interferons-have-opposing-effects-during-the-emergence-and-recovery-phases-of-colitis(e4e85b67-01a1-4985-b926-d9ece082707f).html