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

Abstract

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 β (IL-10Rβ) and an orphan class II receptor chain, designated IL-28Rα. This newly described cytokine family may serve as an alternative to type I IFNs in providing immunity to viral infection.

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Protein Data Bank

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Acknowledgements

We thank P. O'Hara, R. Adams and D. Sawislak for project advice.

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Competing interests

All the authors of the article are employees of ZymoGenetics, Inc. and as such receive salaries and shares of stock in ZymoGenetics.

Correspondence to Kevin M. Klucher.

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Figure 1: Sequence alignment of IL-28 and IL-29.
Figure 2: RNA expression of IL-28 and IL-29.
Figure 3: IFN-like activities of IL-28 and IL-29.
Figure 4: Binding of IL-28A and IL-29.
Figure 5: Alignment of IL-28Rαv1 and IL-22Rα2.
Figure 6: IL-28Rα RNA expression analysis.
Figure 7: Requirement of IL-28Rα and IL-10Rβ for functional signaling.