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Review
. 2019 Feb:56:67-75.
doi: 10.1016/j.coi.2018.10.007. Epub 2018 Nov 3.

Lambda interferons come to light: dual function cytokines mediating antiviral immunity and damage control

Evangelos Andreakos  1 , Ivan Zanoni  2 , Ioanna E Galani  3
Affiliations
Review

Lambda interferons come to light: dual function cytokines mediating antiviral immunity and damage control

Evangelos Andreakos et al. Curr Opin Immunol. 2019 Feb.

Abstract

Lambda interferons (IFNλs, type III IFNs or interleukins-28/29) were described fifteen years ago as novel cytokines sharing structural and functional homology with IL-10 and type I IFNs, respectively. IFNλs engage a unique receptor complex comprising IFNLR1 and IL10R2, nevertheless they share signaling cascade and many functions with type I IFNs, questioning their possible non-redundant roles and overall biological importance. Here, we review the latest evidence establishing the primacy of IFNλs in front line protection at anatomical barriers, mediating antiviral immunity before type I IFNs. We also discuss their emerging role in regulating inflammation and limiting host damage, a major difference to type I IFNs. IFNλs come thus to light as dual function cytokines mediating antiviral immunity and damage control.

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Figures

None
Graphical abstract
Figure 1
Figure 1
Sources and targets of IFNλs among immune and non-immune cell populations. Blue arrows depict cells expressing and red arrows cells responding to IFNλs. MoDC, DC1 and DC2 cells produce IFNλs but only moDC and DC2 cells also respond to them. DCs: Dendritic cells; MoDC: monocyte-derived DCs; DC1: Dendritic cell subset 1; DC 2: Dendritic cell subset 2.
Figure 2
Figure 2
Model of IFNλ action. IFNλs confer initial antiviral protection at anatomical barriers without provoking unnecessary inflammation. Type I IFNs come up as a second line of defense, following escape from IFNλ control, to enhance antiviral and immunoinflammatory responses, at the expense though of collateral damage.
Figure 3
Figure 3
Common and unique structural and functional characteristics of IFNλs with type I IFNs and IL-10. Antiviral activity is shared with type I IFNs whereas immune regulatory and host protective actions are shared with IL-10.
Figure 4
Figure 4
IFNλs as dual function cytokines mediating antiviral activity and damage control. The schematic shows the unique and non-redundant roles of IFNλs in antiviral defense, and their immune regulatory actions mediating disease protection as emerging over the last years.
See this image and copyright information in PMC

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