Type I interferon is required for T helper (Th) 2 induction by dendritic cells

Webb, Lauren M.; Lundie, Rachel J.; Borger, Jessica G.; Brown, Sheila L.; Connor, Lisa M.; Cartwright, Adam N.R.; Dougall, Annette M.; Wilbers, Ruud H.P.; Cook, Peter C.; Jackson-Jones, Lucy H.; Phythian-Adams, Alexander T.; Johansson, Cecilia; Davis, Daniel M.; Dewals, Benjamin G.; Ronchese, Franca; Macdonald, Andrew S.


Type 2 inflammation is a defining feature of infection with parasitic worms (helminths), as well as being responsible for widespread suffering in allergies. However, the precise mechanisms involved in T helper (Th) 2 polarization by dendritic cells (DCs) are currently unclear. We have identified a previously unrecognized role for type I IFN (IFN-I) in enabling this process. An IFN-I signature was evident in DCs responding to the helminth Schistosoma mansoni or the allergen house dust mite (HDM). Further, IFN-I signaling was required for optimal DC phenotypic activation in response to helminth antigen (Ag), and efficient migration to, and localization with, T cells in the draining lymph node (dLN). Importantly, DCs generated from Ifnar1-/- mice were incapable of initiating Th2 responses in vivo. These data demonstrate for the first time that the influence of IFN-I is not limited to antiviral or bacterial settings but also has a central role to play in DC initiation of Th2 responses.