Late Developmental Plasticity in the T Helper 17 Lineage

By Y. Lee, Henrietta Turner, Craig L. Maynard, J. Oliver, Dongquan Chen, C. Elson, C. Weaver. Immunity, 2009

1,122 citations recorded by the source corpus.

SUMMARY Development of T helper (Th) 17 cells requires transforming growth factor (TGF)-β and interleukin (IL)-6 and is independent of the Th1 pathway. Although T cells that produce interferon (IFN)-γ 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-γ-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-β for sustained expression of IL-17F and IL-17A. In the absence of TGF-β, both IL-23 and IL-12 acted to suppress IL-17 and enhance IFN-γ 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 auto-immunity and host defense.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/7104f114bf207b5d610447f62f3347e617550898

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In Immunology

1. Alexander Y. Rudensky
2. Jinfang Zhu
3. W. E. Paul
4. R. Flavell
5. Y. Belkaid
6. V. Kuchroo
7. J. O’Shea
8. Aviv Regev

Citations in the corpus

• Regulation of Insulin Synthesis and Secretion and Pancreatic Beta-Cell Dysfunction in Diabetes (2012, positive): “Studies have shown that Th17 cells may up-regulate IFN-γ and also extinguish IL-17 in response to IL-12 or IL-23 in the absence of TGF-β in vitro and depreciated to a Th17/1 (IL-17+IFN-γ+) or Th1 phenotype [398, 399].”
• CD4+T Cells: Differentiation and Functions (2012, background): “Th17 in the presence of IL12 switched to Th1 phenotype, and interaction with IL4 led to the differentiation into Th2 cells [109, 110].”
• Decrease of Foxp3+ Treg cell number and acquisition of effector cell phenotype during lethal infection (2009, background): “Recent evidence shows that lymphocytes maintain a certain degree of plasticity with respect to their capacity to produce cyto- 782 Immunity 31, 772–786, November 20, 2009 ª2009 Elsevier Inc. kines (Lee et al., 2009; Wei et al., 2009).”
• Expanding roles for CD4+ T cells in immunity to viruses (2012, background): “In vivo , IL-12 can also reprogramme in vitro -polarized T H 17 cells to a T H 1-type phenotyp”
• Th17 cells express interleukin-10 receptor and are controlled by Foxp3− and Foxp3+ regulatory CD4+ T cells in an interleukin-10 dependent manner (2011, background): “An additional point is that most studies of Th17 and also Tr1 cells were based on the use of in vitro differentiated Th17 (Elson et al., 2007; Lee et al., 2009; Wang et al., 2009) or Tr1 (Groux et al., 1997) cells, respectively.”
• Immune adaptations that maintain homeostasis with the intestinal microbiota (2010, background): “A further twist in the complex interactions between T H cell subsets is shown by observations that these subsets are not necessarily terminally differentiated but that there can be conversion from T H 17 to T H 1 cells and T Reg to T H 17 cell”