10.6084/m9.figshare.5125900.v1 Arimori Y. Arimori Y. Nakamura R. Nakamura R. Yamada H. Yamada H. Shibata K. Shibata K. Maeda N. Maeda N. Kase T. Kase T. Yoshikai Y. Yoshikai Y. Supplementary Material for: Type I Interferon Plays Opposing Roles in Cytotoxicity and Interferon-γ Production by Natural Killer and CD8<sup>+</sup> T Cells after Influenza A Virus Infection in Mice Karger Publishers 2014 Natural killer cell CD8+ T cell Interferon-γ Type I interferon Influenza Cytotoxicity 2014-01-10 00:00:00 Dataset https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Type_I_Interferon_Plays_Opposing_Roles_in_Cytotoxicity_and_Interferon-_Production_by_Natural_Killer_and_CD8_sup_sup_T_Cells_after_Influenza_A_Virus_Infection_in_Mice/5125900 Type I interferons (IFNs) promote natural killer (NK) and CD8<sup>+</sup> T-cell responses, which play a role not only in the resolution of infection but also in the induction of acute lung injury following influenza A virus infection. We show here that IFN-α receptor knock-out <i>(Ifnar1</i><sup><i>-/-</i></sup><i>)</i> mice exhibited impaired cytotoxic activity as well as an increased ability of NK and CD8<sup>+</sup> T cells to produce IFN-γ after infection with influenza virus A/FM/1/47 (H1N1, a mouse-adapted strain). A deficiency in IFNAR signaling significantly impaired IL-10 production in influenza virus-infected lungs and enhanced IFN-γ production by NK cells, which were suppressed by exogenous IL-10. Depletion of NK cells but not CD8<sup>+</sup> T cells in <i>Ifnar1</i><sup>-/-</sup> mice improved the survival rate after A/FM/1/47 infection, indicating that NK cells are responsible for acute lung injury in <i>Ifnar1</i><sup>-/-</sup> mice following influenza A virus infection, although the depletion of IFN-γ did not improve the outcome. Thus, type I IFN signaling plays a role not only in the upregulation of cytotoxicity but also in the downregulation of some effector mechanisms including IFN-γ production by NK and CD8<sup>+</sup> T cells via IL-10 production.