For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
58
views
9
references
 Top references
cited by
356
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    1
    shares
      2,986
      similar
       All similar
      • Record: found
      • Abstract: not found
      • Article: not found

      Role of deficient type III interferon-λ production in asthma exacerbations

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Rhinoviruses are the major cause of asthma exacerbations, and asthmatics have increased susceptibility to rhinovirus and risk of invasive bacterial infections. Here we show deficient induction of interferon-lambdas by rhinovirus in asthmatic primary bronchial epithelial cells and alveolar macrophages, which was highly correlated with severity of rhinovirus-induced asthma exacerbation and virus load in experimentally infected human volunteers. Induction by lipopolysaccharide in asthmatic macrophages was also deficient and correlated with exacerbation severity. These results identify previously unknown mechanisms of susceptibility to infection in asthma and suggest new approaches to prevention and/or treatment of asthma exacerbations.

          Related collections

          Most cited references9

          • Record: found
          • Abstract: found
          • Article: not found

          IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex.

          Sergei V. Kotenko, Grant Gallagher, Vitaliy V Baurin … (2003)
          We report here the identification of a ligand-receptor system that, upon engagement, leads to the establishment of an antiviral state. Three closely positioned genes on human chromosome 19 encode distinct but paralogous proteins, which we designate interferon-lambda1 (IFN-lambda1), IFN-lambda2 and IFN-lambda3 (tentatively designated as IL-29, IL-28A and IL-28B, respectively, by HUGO). The expression of IFN-lambda mRNAs was inducible by viral infection in several cell lines. We identified a distinct receptor complex that is utilized by all three IFN-lambda proteins for signaling and is composed of two subunits, a receptor designated CRF2-12 (also designated as IFN-lambdaR1) and a second subunit, CRF2-4 (also known as IL-10R2). Both receptor chains are constitutively expressed on a wide variety of human cell lines and tissues and signal through the Jak-STAT (Janus kinases-signal transducers and activators of transcription) pathway. This receptor-ligand system may contribute to antiviral or other defenses by a mechanism similar to, but independent of, type I IFNs.
          Article 0 comments Cited 557 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            IL-28, IL-29 and their class II cytokine receptor IL-28R.

            Paul Sheppard, Wayne Kindsvogel, Wenfeng Xu … (2003)
            Cytokines play a critical role in modulating the innate and adaptive immune systems. Here, we have identified from the human genomic sequence a family of three cytokines, designated interleukin 28A (IL-28A), IL-28B and IL-29, that are distantly related to type I interferons (IFNs) and the IL-10 family. We found that like type I IFNs, IL-28 and IL-29 were induced by viral infection and showed antiviral activity. However, IL-28 and IL-29 interacted with a heterodimeric class II cytokine receptor that consisted of IL-10 receptor beta (IL-10Rbeta) and an orphan class II receptor chain, designated IL-28Ralpha. This newly described cytokine family may serve as an alternative to type I IFNs in providing immunity to viral infection.
            Article 0 comments Cited 449 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus

              Peter Wark, Sebastian L. Johnston, Fabio Bucchieri … (2005)
              Rhinoviruses are the major trigger of acute asthma exacerbations and asthmatic subjects are more susceptible to these infections. To investigate the underlying mechanisms of this increased susceptibility, we examined virus replication and innate responses to rhinovirus (RV)-16 infection of primary bronchial epithelial cells from asthmatic and healthy control subjects. Viral RNA expression and late virus release into supernatant was increased 50- and 7-fold, respectively in asthmatic cells compared with healthy controls. Virus infection induced late cell lysis in asthmatic cells but not in normal cells. Examination of the early cellular response to infection revealed impairment of virus induced caspase 3/7 activity and of apoptotic responses in the asthmatic cultures. Inhibition of apoptosis in normal cultures resulted in enhanced viral yield, comparable to that seen in infected asthmatic cultures. Examination of early innate immune responses revealed profound impairment of virus-induced interferon-β mRNA expression in asthmatic cultures and they produced >2.5 times less interferon-β protein. In infected asthmatic cells, exogenous interferon-β induced apoptosis and reduced virus replication, demonstrating a causal link between deficient interferon-β, impaired apoptosis and increased virus replication. These data suggest a novel use for type I interferons in the treatment or prevention of virus-induced asthma exacerbations.
              Article 0 comments Cited 404 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Title: Nature Medicine
                Abbreviated Title: Nat Med
                Publisher: Springer Science and Business Media LLC
                ISSN (Print): 1078-8956
                ISSN (Electronic): 1546-170X
                Publication date Created: September 2006
                Publication date (Electronic): August 13 2006
                Publication date (Print): September 2006
                Volume: 12
                Issue: 9
                Pages: 1023-1026
                Article
                DOI: 10.1038/nm1462
                PubMed ID: 16906156
                SO-VID: e8b11593-8191-4ab5-974a-d2cc568a21e3
                Copyright © © 2006
                License:

                http://www.springer.com/tdm

                History

                Data availability:

                Comments

                Comment on this article

                scite_

                Similar content2,986

                See all similar

                Cited by341

                See all cited by