Type I interferon is required for T helper (Th) 2 induction by dendritic cells. (17th July 2017)

• Record Type: Journal Article
• Authors: Webb, Lauren M; Lundie, Rachel J; Borger, Jessica G; Brown, Sheila L; Connor, Lisa M; Cartwright, Adam NR; Dougall, Annette M; Wilbers, Ruud HP; Cook, Peter C; Jackson‐Jones, Lucy H; Phythian‐Adams, Alexander T; Johansson, Cecilia; Davis, Daniel M; Dewals, Benjamin G; Ronchese, Franca; MacDonald, Andrew S
• Is Part Of: EMBO journal. Volume 36:Number 16(2017)
• Page Start: 2404
• Page End: 2418
• Publication Date: 2017-07-17
• Subjects: dendritic cell -- interferon -- priming -- Th2; Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.201695345
• Languages: English
• ISSNs: 0261-4189

Abstract

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. Synopsis: Type I interferon (IFN‐I) mediates conventional dendritic cell (cDC) activation in a type 2 inflammatory response to parasitic worm infection or the allergen house dust mite, supporting T‐helper 2 (Th2) cell induction. cDCs respond to type 2 antigens by producing IFN‐I and expressing interferon‐stimulated genes. Ifnar1 −/− cDCs display reduced phenotypic activation and cytokine production in response to type 2 antigens, indicating that cDC responsiveness to IFN‐I is required for this process. Ifnar1 −/− cDCs display reduced migration in vivo, indicating that cDC responsiveness to IFN‐I is required for this process. Ifnar1 −/− cDCs display reduced ability to initiate Th2 responses in vivo, indicating that cDC responsiveness to IFN‐I is required for this process. Abstract : Type I interferon (IFN‐I) mediates dendritic cell (cDC) activation in a type 2 inflammatory response to parasitic worm infection or the allergen house dust mite, supporting T‐helper 2 (Th2) cell induction.