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

doi:10.15252/embj.201695345

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

50 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 language	English
Pages (from-to)	2404-2418
Journal	The EMBO Journal
Volume	36
Issue number	16
DOIs	https://doi.org/10.15252/embj.201695345
Publication status	Published - 2017

Keywords

Dendritic cell
Interferon
Priming
Th2

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Webb, L. M., Lundie, R. J., Borger, J. G., Brown, S. L., Connor, L. M., Cartwright, A. N. R., Dougall, A. M., Wilbers, R. H. P., Cook, P. C., Jackson-Jones, L. H., Phythian-Adams, A. T., Johansson, C., Davis, D. M., Dewals, B. G., Ronchese, F., & Macdonald, A. S. (2017). Type I interferon is required for T helper (Th) 2 induction by dendritic cells. The EMBO Journal, 36(16), 2404-2418. https://doi.org/10.15252/embj.201695345

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

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.",

keywords = "Dendritic cell, Interferon, Priming, Th2",

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

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doi = "10.15252/embj.201695345",

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Webb, LM, Lundie, RJ, Borger, JG, Brown, SL, Connor, LM, Cartwright, ANR, Dougall, AM, Wilbers, RHP, Cook, PC, Jackson-Jones, LH, Phythian-Adams, AT, Johansson, C, Davis, DM, Dewals, BG, Ronchese, F & Macdonald, AS 2017, 'Type I interferon is required for T helper (Th) 2 induction by dendritic cells', The EMBO Journal, vol. 36, no. 16, pp. 2404-2418. https://doi.org/10.15252/embj.201695345

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T1 - Type I interferon is required for T helper (Th) 2 induction by dendritic cells

AU - Webb, Lauren M.

AU - Lundie, Rachel J.

AU - Borger, Jessica G.

AU - Brown, Sheila L.

AU - Connor, Lisa M.

AU - Cartwright, Adam N.R.

AU - Dougall, Annette M.

AU - Wilbers, Ruud H.P.

AU - Cook, Peter C.

AU - Jackson-Jones, Lucy H.

AU - Phythian-Adams, Alexander T.

AU - Johansson, Cecilia

AU - Davis, Daniel M.

AU - Dewals, Benjamin G.

AU - Ronchese, Franca

AU - Macdonald, Andrew S.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Dendritic cell

KW - Interferon

KW - Priming

KW - Th2

U2 - 10.15252/embj.201695345

DO - 10.15252/embj.201695345

M3 - Article

AN - SCOPUS:85024114576

VL - 36

SP - 2404

EP - 2418

JO - The EMBO Journal

JF - The EMBO Journal

SN - 0261-4189

IS - 16

ER -

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

Abstract

Keywords

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