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Th17 cells: a new fate for differentiating helper T cells

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Abstract

Classically naïve CD4+ have been thought to differentiate into two possible lineages, T helper 1 (Th1) or T helper 2 (Th2) cells. Within this paradigm the pathogenesis of autoimmunity was suggested to predominantly relate to Th1 cells and the production of IFN-γ. However, there were many aspects of this model that did not seem to fit, not the least of which was that IFN-γ was protective in some models of autoimmunity. During the past 2 years, remarkable progress has been made to characterize a new lineage of helper T cells. Designated Th17 cells, this lineage selectively produces proinflammatory cytokines including IL-17, IL-21, and IL-22. In the mouse, the differentiation of this new lineage is initiated by TGFβ-1 and IL-6 and IL-21, which activate Stat3 and induce the expression of the transcription factor retinoic acid-related orphan receptor (RORγt). IL-23, which also activates Stat3, apparently serves to maintain Th17 cells in vivo. In human cells, IL-1, IL-6, and IL-23 promote human Th17 differentiation, but TGFβ-1 is reportedly not needed. Emerging data have suggested that Th17 plays an essential role in the host defense against extracellular bacteria and fungi and in pathogenesis of autoimmune diseases. Selectively targeting the Th17 lineage may be beneficial for the treatment of inflammatory and autoimmune diseases.

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Notes

  1. Recent evidence indicates that Th17 cells can also make IL-10 and IL-23 is an important factor that regulates the pathogenicity of Th17 cells.

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Authors and Affiliations

  1. Molecular Immunology and Inflammation Branch, National Institutes of Arthritis, Musculoskeletal and Skin Diseases, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA

    Zhi Chen & John J. O’Shea

  2. Faculty of Medicine, Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520, Turku, Finland

    Zhi Chen & John J. O’Shea

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  1. Zhi Chen
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  2. John J. O’Shea
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Correspondence to Zhi Chen.

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Chen, Z., O’Shea, J.J. Th17 cells: a new fate for differentiating helper T cells. Immunol Res 41, 87–102 (2008). https://doi.org/10.1007/s12026-007-8014-9

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  • DOI: https://doi.org/10.1007/s12026-007-8014-9

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