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Late developmental plasticity in the T helper 17 lineage.

Immunity | Jan 16, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19119024

Development of T helper (Th) 17 cells requires transforming growth factor (TGF)-beta and interleukin (IL)-6 and is independent of the Th1 pathway. Although T cells that produce interferon (IFN)-gamma are a recognized feature of Th17 cell responses, mice deficient for STAT4 and T-bet-two prototypical Th1 transcription factors-are protected from autoimmunity associated with Th17 pathogenesis. To examine the fate and pathogenic potential of Th17 cells and origin of IFN-gamma-producing T cells that emerge during Th17 immunity, we developed IL-17F reporter mice that identify cells committed to expression of IL-17F and IL-17A. Th17 cells required TGF-beta for sustained expression of IL-17F and IL-17A. In the absence of TGF-beta, both IL-23 and IL-12 acted to suppress IL-17 and enhance IFN-gamma production in a STAT4- and T-bet-dependent manner, albeit with distinct efficiencies. These results support a model of late Th17 developmental plasticity with implications for autoimmunity and host defense.

Pubmed ID: 19119024 RIS Download

Mesh terms: Animals | Cell Lineage | Cells, Cultured | Flow Cytometry | Interferon-gamma | Interleukin-17 | Interleukin-23 | Mice | Mice, Knockout | T-Lymphocyte Subsets | Th1 Cells | Th2 Cells | Transforming Growth Factor beta

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Associated grants

  • Agency: NIDDK NIH HHS, Id: P01 DK071176
  • Agency: NIDDK NIH HHS, Id: P01 DK071176-01
  • Agency: NIDDK NIH HHS, Id: P01 DK071176-02
  • Agency: NIDDK NIH HHS, Id: P01 DK071176-03
  • Agency: NIDDK NIH HHS, Id: P01 DK071176-04
  • Agency: NIDDK NIH HHS, Id: P01 DK071176-04S1
  • Agency: NIDDK NIH HHS, Id: P01 DK071176-05
  • Agency: NIDDK NIH HHS, Id: P01 DK071176-06
  • Agency: NIDDK NIH HHS, Id: P01 DK071176-07
  • Agency: NIDDK NIH HHS, Id: P01 DK071176-08
  • Agency: NIAID NIH HHS, Id: R01 AI035783
  • Agency: NIAID NIH HHS, Id: R01 AI077574
  • Agency: NIAID NIH HHS, Id: R01 AI077574-01A2
  • Agency: NIAID NIH HHS, Id: R01 AI077574-02
  • Agency: NIAID NIH HHS, Id: R01 AI077574-03
  • Agency: NIAID NIH HHS, Id: R01 AI077574-04
  • Agency: NIDDK NIH HHS, Id: R24 DK064400

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