Research ArticleINNATE IMMUNITY

Selective Janus kinase inhibition preserves interferon-λ–mediated antiviral responses

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Science Immunology  14 May 2021:
Vol. 6, Issue 59, eabd5318
DOI: 10.1126/sciimmunol.abd5318

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Specific inhibition

Janus kinase (JAK) inhibitors are powerful therapeutics used to treat inflammatory diseases but are also linked to immune suppression and complications associated with viral infections. Schnepf et al. show that selective inhibition of tyrosine kinase 2 (TYK2) can block potentially noxious type I IFN signaling but does not alter IFN-λ signaling, whereas the JAK1/2 inhibitor baricitinib blocks both types of IFN responses. Epithelial cells did not require TYK2 for IFN-λ–driven gene expression or antiviral responses, and TYK2-deficient mice have intact IFN-λ–mediated responses and are protected from influenza A virus infection. These findings indicate that TYK2 inhibition may be a better treatment option for type I interferonopathies.

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