Interferon-λ enhances adaptive mucosal immunity by boosting release of thymic stromal lymphopoietin

Liang Ye, Daniel Schnepf, Jan Becker, Karolina Ebert, Yakup Tanriver, Valentina Bernasconi, Hans Henrik Gad, Rune Hartmann, Nils Lycke, Peter Staeheli

    Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

    Abstract

    Interferon-λ (IFN-λ) acts on mucosal epithelial cells and thereby confers direct antiviral protection. In contrast, the role of IFN-λ in adaptive immunity is far less clear. Here, we report that mice deficient in IFN-λ signaling exhibited impaired CD8+ T cell and antibody responses after infection with a live-attenuated influenza virus. Virus-induced release of IFN-λ triggered the synthesis of thymic stromal lymphopoietin (TSLP) by M cells in the upper airways that, in turn, stimulated migratory dendritic cells and boosted antigen-dependent germinal center reactions in draining lymph nodes. The IFN-λ-TSLP axis also boosted production of the immunoglobulins IgG1 and IgA after intranasal immunization with influenza virus subunit vaccines and improved survival of mice after challenge with virulent influenza viruses. IFN-λ did not influence the efficacy of vaccines applied by subcutaneous or intraperitoneal routes, indicating that IFN-λ plays a vital role in potentiating adaptive immune responses that initiate at mucosal surfaces.

    OriginalsprogEngelsk
    TidsskriftNature Immunology
    Vol/bind20
    Nummer5
    Sider (fra-til)593-601
    Antal sider9
    ISSN1529-2908
    DOI
    StatusUdgivet - maj 2019

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