Abstract
Type 17 T helper (TH17) cells are a population of CD4+ effector T cells that are distinct from TH1 and TH2 cells owing to their ability to produce interleukin (IL)-17. Although TH1 and TH2 cells are similar in mice and humans, TH17 cells differ in several ways. The differentiation of mouse TH17 cells requires transforming growth factor β and IL-6, whereas human naive T cells can develop into TH17 cells in the presence of IL-1β and IL-23 alone, transforming growth factor β having an indirect role in their development via the selective inhibition of TH1 cell expansion. In both mice and humans, a late developmental plasticity of TH17 cells towards the TH1 lineage has been shown. Mainly based on mouse gene knockout studies, TH17 lymphocytes have been found to have a pathogenic role in several autoimmune disorders; however, whether human autoimmune disorders, including rheumatoid arthritis (RA) and psoriasis, are prevalently TH1-mediated or TH17-mediated, is still unclear. Research suggests that both TH1 and TH17 cells are involved in RA pathogenesis, raising the possibility that interventions that target both the IL-23–IL-17 (TH17) and the IL-12–interferon γ (TH1) axes might be successful future therapeutic approaches for RA.
Key Points
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It is our opinion that the origin and development of type 17 T helper (TH17) cells in humans is different than in mice
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Human TH17 cells can be induced to produce interferon-γ in the presence of interleukin (IL)-12, thus becoming TH17/TH1 cells
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TH17 cells are associated with several immune-mediated diseases, particularly psoriasis and rheumatoid arthritis, owing to the pleiotropic effects exerted by IL-17 and related-cytokines on osteoblasts, B cells and monocytes
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The pathogenesis of rheumatoid arthritis is more complex than previously thought; both TH17 and TH1 cells are probably involved in the maintenance of inflammation that leads to joint destruction
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Immune-mediated diseases could perhaps be treated more effectively by therapeutic interventions that target both the IL-23–IL-17 (TH17) and IL12–interferon-γ (TH1) axes, rather than just a single pathway
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Acknowledgements
The studies by F. Annunziato, L. Cosmi, F. Liotta, E. Maggi and S. Romagnani discussed in this Review have been supported by funds from the Italian Ministry of Education (40%), the Italian Ministry of Health, the Ente Cassa di Risparmio of Florence, and EU Projects SENS-IT-IV and INNOCHEM.
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Annunziato, F., Cosmi, L., Liotta, F. et al. Type 17 T helper cells—origins, features and possible roles in rheumatic disease. Nat Rev Rheumatol 5, 325–331 (2009). https://doi.org/10.1038/nrrheum.2009.80
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DOI: https://doi.org/10.1038/nrrheum.2009.80
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