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

doi:10.1038/s41590-019-0345-x

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 avis › Tidsskriftartikel › Forskning › peer review

72 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Nature Immunology
Vol/bind	20
Nummer	5
Sider (fra-til)	593-601
Antal sider	9
ISSN	1529-2908
DOI	https://doi.org/10.1038/s41590-019-0345-x
Status	Udgivet - maj 2019

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10.1038/s41590-019-0345-x

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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.",

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author = "Liang Ye and Daniel Schnepf and Jan Becker and Karolina Ebert and Yakup Tanriver and Valentina Bernasconi and Gad, {Hans Henrik} and Rune Hartmann and Nils Lycke and Peter Staeheli",

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AU - Ye, Liang

AU - Schnepf, Daniel

AU - Becker, Jan

AU - Ebert, Karolina

AU - Tanriver, Yakup

AU - Bernasconi, Valentina

AU - Gad, Hans Henrik

AU - Hartmann, Rune

AU - Lycke, Nils

AU - Staeheli, Peter

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N2 - 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.

AB - 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.

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KW - Influenza A virus/drug effects

KW - Influenza Vaccines/administration & dosage

KW - Interleukins/administration & dosage

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KW - Mice, Inbred C57BL

KW - Mice, Inbred DBA

KW - Mice, Knockout

KW - Orthomyxoviridae Infections/immunology

KW - Receptors, Interferon/genetics

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ER -

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

Abstract

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