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

Webb, Lauren M and Lundie, Rachel J and Borger, Jessica G and Brown, Sheila L and Connor, Lisa M and Cartwright, Adam Nr and Dougall, Annette M and Wilbers, Ruud Hp and Cook, Peter C and Jackson-Jones, Lucy H and Phythian-Adams, Alexander T and Johansson, Cecilia and Davis, Daniel M and Dewals, Benjamin G and Ronchese, Franca and MacDonald, Andrew S (2017) Type I interferon is required for T helper (Th) 2 induction by dendritic cells. EMBO Journal, 36 (16). pp. 2404-2418. ISSN 0261-4189

Abstract

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.