title: Type I interferons have opposing effects during the emergence and recovery phases of colitis.
abstract: 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.
authors: Max F. Perutz Laboratories, Department of Microbiology, Immunobiology and Genetics, University of Vienna, Vienna, Austria.
authors: Isabella
authors: I
authors: Rauch
authors: Eva
authors: E
authors: Hainzl
authors: Felix
authors: F
authors: Rosebrock
authors: Susanne
authors: S
authors: Heider
authors: Clarissa
authors: C
authors: Schwab
authors: David
authors: D
authors: Berry
authors: Dagmar
authors: D
authors: Stoiber
authors: Michael
authors: M
authors: Wagner
authors: Christa
authors: C
authors: Schleper
authors: Alexander
authors: A
authors: Loy
authors: Tim
authors: T
authors: Urich
authors: Mathias
authors: M
authors: Müller
authors: Birgit
authors: B
authors: Strobl
authors: Lukas
authors: L
authors: Kenner
authors: Thomas
authors: T
authors: Decker
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology*; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D007422:Intestines / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000473:pathology
chemical_list: D000949:Histocompatibility Antigens Class II; D007370:Interferon Type I; D053583:Interleukin-1beta; D016264:Dextran Sulfate
keywords: Colitis; Inflammation; Interferons; Interleukin-1; Microbiota