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Late developmental plasticity in the T helper 17 lineage.

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

Authors

  • Lee YK
  • Turner H
  • Maynard CL
  • Oliver JR
  • Chen D
  • Elson CO
  • Weaver CT

Journal

Immunity

Publication Data

January 16, 2009

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

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