251. IFN-λ suppresses intestinal inflammation by non-translational regulation of neutrophil function.
- Author
-
Broggi A, Tan Y, Granucci F, and Zanoni I
- Subjects
- Animals, Cluster Analysis, Disease Models, Animal, Gastroenteritis pathology, Gene Expression, Gene Expression Profiling, Gene Expression Regulation, Genetic Predisposition to Disease, Humans, Intestinal Mucosa immunology, Intestinal Mucosa microbiology, Intestinal Mucosa pathology, Intestines pathology, Mice, Mice, Knockout, Microbiota, Oxidative Stress, Receptors, Cytokine genetics, Receptors, Cytokine metabolism, Gastroenteritis etiology, Gastroenteritis metabolism, Interferon-gamma metabolism, Intestinal Mucosa metabolism, Intestines immunology, Neutrophils immunology, Neutrophils metabolism
- Abstract
Interferon-λ (IFN-λ) is a central regulator of mucosal immunity; however, its signaling specificity relative to that of type I interferons is poorly defined. IFN-λ can induce antiviral interferon-stimulated genes (ISGs) in epithelia, while the effect of IFN-λ in non-epithelial cells remains unclear. Here we report that neutrophils responded to IFN-λ. We found that in addition to inducing ISG transcription, IFN-λ (but not IFN-β) specifically activated a translation-independent signaling pathway that diminished the production of reactive oxygen species and degranulation in neutrophils. In mice, IFN-λ was elicited by enteric viruses and acted on neutrophils to decrease oxidative stress and intestinal damage. Thus, IFN-λ acted as a unique immunomodulatory agent by modifying transcriptional and non-translational neutrophil responses, which might permit a controlled development of the inflammatory process.
- Published
- 2017
- Full Text
- View/download PDF