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

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

Research output: Contribution to journalArticlepeer-review

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
JournalEMBO Journal
Early online date17 Jul 2017
DOIs
Publication statusE-pub ahead of print - 17 Jul 2017

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