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

Research output: Contribution to journalArticleResearchpeer-review

13 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
JournalEMBO Journal
Volume36
DOIs
Publication statusPublished - 17 Jul 2017
Externally publishedYes

Keywords

  • Dendritic cell
  • Interferon
  • Priming
  • Th2

Cite this

Webb, L. M., Lundie, R. J., Borger, J. G., Brown, S. L., Connor, L. M., Cartwright, A. N. R., ... Macdonald, A. S. (2017). Type I interferon is required for T helper (Th) 2 induction by dendritic cells. EMBO Journal, 36, 2404-2418. https://doi.org/10.15252/embj.201695345
Webb, Lauren M ; Lundie, Rachel J ; Borger, Jessica G. ; Brown, Sheila L. ; Connor, Lisa M. ; Cartwright, Adam N.R. ; Dougall, Annette M. ; Wilbers, Ruud H.P. ; Cook, Peter C. ; Jackson-Jones, Lucy H. ; Phythian-Adams, Alexander T. ; Johansson, Cecilia ; Davis, Daniel M. ; Dewals, Benjamin G. ; Ronchese, Franca ; Macdonald, Andrew S. / Type I interferon is required for T helper (Th) 2 induction by dendritic cells. In: EMBO Journal. 2017 ; Vol. 36. pp. 2404-2418.
@article{baccde7cf3f9426b822c6d75881b81e4,
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.}",
year = "2017",
month = "7",
day = "17",
doi = "10.15252/embj.201695345",
language = "English",
volume = "36",
pages = "2404--2418",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "John Wiley & Sons",

}

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', EMBO Journal, vol. 36, pp. 2404-2418. https://doi.org/10.15252/embj.201695345

Type I interferon is required for T helper (Th) 2 induction by dendritic cells. / Webb, Lauren M; Lundie, Rachel J; Borger, Jessica G.; Brown, Sheila L.; Connor, Lisa M.; Cartwright, Adam N.R.; Dougall, Annette M.; Wilbers, Ruud H.P.; Cook, Peter C.; Jackson-Jones, Lucy H.; Phythian-Adams, Alexander T.; Johansson, Cecilia; Davis, Daniel M.; Dewals, Benjamin G.; Ronchese, Franca; Macdonald, Andrew S.

In: EMBO Journal, Vol. 36, 17.07.2017, p. 2404-2418.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

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 - 2017/7/17

Y1 - 2017/7/17

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

UR - http://www.scopus.com/inward/record.url?scp=85024114576&partnerID=8YFLogxK

U2 - 10.15252/embj.201695345

DO - 10.15252/embj.201695345

M3 - Article

VL - 36

SP - 2404

EP - 2418

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

ER -