tetano
Editor, Senior Moderator
Nat Immunol. 2019 Jun 24. doi: 10.1038/s41590-019-0408-z. [Epub ahead of print]
[h=1]Interferon-λ modulates dendritic cells to facilitate T cell immunity during infection with influenza A virus.[/h] Hemann EA[SUP]1[/SUP], Green R[SUP]1[/SUP], Turnbull JB[SUP]1[/SUP], Langlois RA[SUP]2[/SUP], Savan R[SUP]1[/SUP], Gale M Jr[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Type III interferon (IFN-λ) is important for innate immune protection at mucosal surfaces and has therapeutic benefit against influenza A virus (IAV) infection. However, the mechanisms by which IFN-λ programs adaptive immune protection against IAV are undefined. Here we found that IFN-λ signaling in dendritic cell (DC) populations was critical for the development of protective IAV-specific CD8[SUP]+[/SUP] T cell responses. Mice lacking the IFN-λ receptor (Ifnlr1[SUP]-/-[/SUP]) had blunted CD8[SUP]+[/SUP] T cell responses relative to wild type and exhibited reduced survival after heterosubtypic IAV re-challenge. Analysis of DCs revealed IFN-λ signaling directed the migration and function of CD103[SUP]+[/SUP] DCs for development of optimal antiviral CD8[SUP]+[/SUP] T cell responses, and bioinformatic analyses identified IFN-λ regulation of a DC IL-10 immunoregulatory network. Thus, IFN-λ serves a critical role in bridging innate and adaptive immunity from lung mucosa to lymph nodes to program DCs to direct effective T cell immunity against IAV.
PMID: 31235953 DOI: 10.1038/s41590-019-0408-z
[h=1]Interferon-λ modulates dendritic cells to facilitate T cell immunity during infection with influenza A virus.[/h] Hemann EA[SUP]1[/SUP], Green R[SUP]1[/SUP], Turnbull JB[SUP]1[/SUP], Langlois RA[SUP]2[/SUP], Savan R[SUP]1[/SUP], Gale M Jr[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Type III interferon (IFN-λ) is important for innate immune protection at mucosal surfaces and has therapeutic benefit against influenza A virus (IAV) infection. However, the mechanisms by which IFN-λ programs adaptive immune protection against IAV are undefined. Here we found that IFN-λ signaling in dendritic cell (DC) populations was critical for the development of protective IAV-specific CD8[SUP]+[/SUP] T cell responses. Mice lacking the IFN-λ receptor (Ifnlr1[SUP]-/-[/SUP]) had blunted CD8[SUP]+[/SUP] T cell responses relative to wild type and exhibited reduced survival after heterosubtypic IAV re-challenge. Analysis of DCs revealed IFN-λ signaling directed the migration and function of CD103[SUP]+[/SUP] DCs for development of optimal antiviral CD8[SUP]+[/SUP] T cell responses, and bioinformatic analyses identified IFN-λ regulation of a DC IL-10 immunoregulatory network. Thus, IFN-λ serves a critical role in bridging innate and adaptive immunity from lung mucosa to lymph nodes to program DCs to direct effective T cell immunity against IAV.
PMID: 31235953 DOI: 10.1038/s41590-019-0408-z