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

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

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31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2404-2418
Number of pages15
JournalThe EMBO Journal
Volume36
DOIs
Publication statusPublished - 17 Jul 2017
Externally publishedYes

Keywords

  • Dendritic cell
  • Interferon
  • Priming
  • Th2

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