Brucklacher-Waldert, Verena, Ferreira, Cristina, Innocentin, Silvia et al. (4 more authors) (2016) Tbet or Continued RORγt Expression Is Not Required for Th17-Associated Immunopathology. Journal of Immunology. pp. 4893-4904. ISSN 1550-6606
Abstract
The discovery of Th17 cell plasticity, in which CD4 + IL-17-producing Th17 cells give rise to IL-17/IFN-γ double-producing cells and Th1-like IFNγ+ ex-Th17 lymphocytes, has raised questions regarding which of these cell types contribute to immunopathology during inflammatory diseases. In this study, we show using Helicobacter hepaticus-induced intestinal inflammation that IL-17ACre- or Rag1Cre-mediated deletion of Tbx21 has no effect on the generation of IL-17/IFN-g double-producing cells, but leads to a marked absence of Th1-like IFNγ+ ex-Th17 cells. Despite the lack of Th1-like ex-Th17 cells, the degree of H. hepaticus-Triggered intestinal inflammation in mice in which Tbx21 was excised in IL-17-producing or Rag1-expressing cells is indistinguishable from that observed in control mice. In stark contrast, using experimental autoimmune encephalomyelitis, we show that IL-17ACre-mediated deletion of Tbx21 prevents the conversion of Th17 cells to IL-17A/IFN-γ double-producing cells as well as Th1-like IFN-γ+ ex-Th17 cells. However, IL-17ACre-mediated deletion of Tbx21 has only limited effects on disease course in this model and is not compensated by Ag-specific Th1 cells. IL-17ACre-mediated deletion of Rorc reveals that RORγt is essential for the maintenance of the Th17 cell lineage, but not immunopathology during experimental autoimmune encephalomyelitis. These results show that neither the single Th17 subset, nor its progeny, is solely responsible for immunopathology or autoimmunity.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2016 The Authors |
Dates: |
|
Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Hull York Medical School (York) |
Depositing User: | Pure (York) |
Date Deposited: | 05 Jul 2016 08:32 |
Last Modified: | 23 Jan 2025 00:07 |
Published Version: | https://doi.org/10.4049/jimmunol.1600137 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.4049/jimmunol.1600137 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:101973 |
Download
Filename: J_Immunol_2016_Brucklacher_Waldert_4893_904.pdf
Description: J Immunol-2016-Brucklacher-Waldert-4893-904
Licence: CC-BY 2.5