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Tbet or Continued RORγt Expression Is Not Required for Th17-Associated Immunopathology.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2016 Jun 15; Vol. 196 (12), pp. 4893-904. Date of Electronic Publication: 2016 May 11. - Publication Year :
- 2016
-
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-17A(Cre)- or Rag1(Cre)-mediated deletion of Tbx21 has no effect on the generation of IL-17/IFN-γ 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-17A(Cre)-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-17A(Cre)-mediated deletion of Tbx21 has only limited effects on disease course in this model and is not compensated by Ag-specific Th1 cells. IL-17A(Cre)-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.<br /> (Copyright © 2016 The Authors.)
- Subjects :
- Animals
CD4-Positive T-Lymphocytes immunology
Cell Differentiation
Encephalomyelitis, Autoimmune, Experimental immunology
Encephalomyelitis, Autoimmune, Experimental physiopathology
Helicobacter hepaticus immunology
Interferon-gamma biosynthesis
Interleukin-17 immunology
Intestines immunology
Intestines microbiology
Intestines pathology
Mice
Mice, Inbred C57BL
Mice, Knockout
Nuclear Receptor Subfamily 1, Group F, Member 3 deficiency
Nuclear Receptor Subfamily 1, Group F, Member 3 genetics
T-Box Domain Proteins deficiency
T-Box Domain Proteins genetics
Th17 Cells pathology
Enteritis immunology
Nuclear Receptor Subfamily 1, Group F, Member 3 metabolism
T-Box Domain Proteins metabolism
Th17 Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 196
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 27183623
- Full Text :
- https://doi.org/10.4049/jimmunol.1600137