Interferon (IFN)-λ Takes the Helm: Immunomodulatory Roles of Type III IFNs
Type III interferons (IFNs) (or IFN-λ) are the latest addition to the IFN family. Even though they share little protein homology with type I IFN, both exhibit remarkable functional similarities: each can be induced in response to viral infections, and both lead to Janus kinases (JAK) and signal tran...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01661/full |
| _version_ | 1818555598586773504 |
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| author | Ivan Zanoni Ivan Zanoni Francesca Granucci Achille Broggi |
| author_facet | Ivan Zanoni Ivan Zanoni Francesca Granucci Achille Broggi |
| author_sort | Ivan Zanoni |
| collection | DOAJ |
| description | Type III interferons (IFNs) (or IFN-λ) are the latest addition to the IFN family. Even though they share little protein homology with type I IFN, both exhibit remarkable functional similarities: each can be induced in response to viral infections, and both lead to Janus kinases (JAK) and signal transducer and activator of transcription (STAT) activation. The JAK/STAT pathway induces antiviral responses and IFN-stimulated gene transcription. However, despite the similarities in their effector functions with type I IFNs, IFN-λ also has a non-redundant role in protecting barrier organs: epithelial cells preferentially produce IFN-λ rather than type I IFNs; and interferon lambda receptor 1 (IFNLR1), the specific receptor for IFN-λ, is highly expressed on cells of epithelial lineage. Thus far, IFN-λ has been considered mainly as an epithelial cytokine, which restricts viral replication in epithelial cells and constitutes an added layer of protection at mucosal sites. However, it is now increasingly recognized that IFNLR1 is expressed broadly, and that immune cells such as neutrophils and dendritic cells also respond to IFN-λ. Moreover, in many in vivo models, IFN-λ modulates immune cell functions and thereby configures itself less as a cytokine that is only specific to the epithelium, and more as a cytokine that directly controls the inflammatory response at mucosal sites. Here, we critically review the recent literature on immune modulatory roles for IFN-λ, and distinguish between the direct and indirect effects of this IFN on immune cell functions in different inflammatory settings. |
| first_indexed | 2024-12-12T09:55:32Z |
| format | Article |
| id | doaj.art-50711a1d01e84f198a006991d22d0002 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T09:55:32Z |
| publishDate | 2017-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-50711a1d01e84f198a006991d22d00022022-12-22T00:28:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-11-01810.3389/fimmu.2017.01661319732Interferon (IFN)-λ Takes the Helm: Immunomodulatory Roles of Type III IFNsIvan Zanoni0Ivan Zanoni1Francesca Granucci2Achille Broggi3Harvard Medical School, Division of Gastroenterology, Boston Children’s Hospital, Boston, MA, United StatesDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, ItalyDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, ItalyHarvard Medical School, Division of Gastroenterology, Boston Children’s Hospital, Boston, MA, United StatesType III interferons (IFNs) (or IFN-λ) are the latest addition to the IFN family. Even though they share little protein homology with type I IFN, both exhibit remarkable functional similarities: each can be induced in response to viral infections, and both lead to Janus kinases (JAK) and signal transducer and activator of transcription (STAT) activation. The JAK/STAT pathway induces antiviral responses and IFN-stimulated gene transcription. However, despite the similarities in their effector functions with type I IFNs, IFN-λ also has a non-redundant role in protecting barrier organs: epithelial cells preferentially produce IFN-λ rather than type I IFNs; and interferon lambda receptor 1 (IFNLR1), the specific receptor for IFN-λ, is highly expressed on cells of epithelial lineage. Thus far, IFN-λ has been considered mainly as an epithelial cytokine, which restricts viral replication in epithelial cells and constitutes an added layer of protection at mucosal sites. However, it is now increasingly recognized that IFNLR1 is expressed broadly, and that immune cells such as neutrophils and dendritic cells also respond to IFN-λ. Moreover, in many in vivo models, IFN-λ modulates immune cell functions and thereby configures itself less as a cytokine that is only specific to the epithelium, and more as a cytokine that directly controls the inflammatory response at mucosal sites. Here, we critically review the recent literature on immune modulatory roles for IFN-λ, and distinguish between the direct and indirect effects of this IFN on immune cell functions in different inflammatory settings.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01661/fullinterferon lambdadendritic cellsneutrophilsnatural killer cellstype III interferonviral infection |
| spellingShingle | Ivan Zanoni Ivan Zanoni Francesca Granucci Achille Broggi Interferon (IFN)-λ Takes the Helm: Immunomodulatory Roles of Type III IFNs Frontiers in Immunology interferon lambda dendritic cells neutrophils natural killer cells type III interferon viral infection |
| title | Interferon (IFN)-λ Takes the Helm: Immunomodulatory Roles of Type III IFNs |
| title_full | Interferon (IFN)-λ Takes the Helm: Immunomodulatory Roles of Type III IFNs |
| title_fullStr | Interferon (IFN)-λ Takes the Helm: Immunomodulatory Roles of Type III IFNs |
| title_full_unstemmed | Interferon (IFN)-λ Takes the Helm: Immunomodulatory Roles of Type III IFNs |
| title_short | Interferon (IFN)-λ Takes the Helm: Immunomodulatory Roles of Type III IFNs |
| title_sort | interferon ifn λ takes the helm immunomodulatory roles of type iii ifns |
| topic | interferon lambda dendritic cells neutrophils natural killer cells type III interferon viral infection |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01661/full |
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