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.

Broggi, A., Tan, Y., Granucci, F., & Zanoni, I. (2017). IFN-λ suppresses intestinal inflammation by non-translational regulation of neutrophil function. NATURE IMMUNOLOGY, 18(10), 1084-1093 [10.1038/ni.3821].

IFN-λ suppresses intestinal inflammation by non-translational regulation of neutrophil function

Broggi, A;Granucci, F
;
Zanoni, I.
2017

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.
Si
Articolo in rivista - Articolo scientifico
Scientifica
Animals; Cluster Analysis; Disease Models, Animal; Gastroenteritis; Gene Expression; Gene Expression Profiling; Gene Expression Regulation; Genetic Predisposition to Disease; Humans; Interferon-gamma; Intestinal Mucosa; Intestines; Mice; Mice, Knockout; Microbiota; Neutrophils; Oxidative Stress; Receptors, Cytokine; Immunology
English
1084
1093
10
Broggi, A., Tan, Y., Granucci, F., & Zanoni, I. (2017). IFN-λ suppresses intestinal inflammation by non-translational regulation of neutrophil function. NATURE IMMUNOLOGY, 18(10), 1084-1093 [10.1038/ni.3821].
Broggi, A; Tan, Y; Granucci, F; Zanoni, I
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/175830
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