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International Immunology Advance Access originally published online on September 26, 2008
International Immunology 2008 20(11):1361-1368; doi:10.1093/intimm/dxn106
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© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

review-article

The phenotype of human Th17 cells and their precursors, the cytokines that mediate their differentiation and the role of Th17 cells in inflammation

Francesco Annunziato, Lorenzo Cosmi, Francesco Liotta, Enrico Maggi and Sergio Romagnani

Center of Excellence for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies, University of Florence, Florence, Italy

Correspondence to: S. Romagnani, Department of Internal Medicine, University of Florence, Viale Morgagni 85, Firenze 50134, Italy; E-mail: s.romagnani{at}dmi.unifi.it

T helper 17 (Th17) cells represent a new subset of CD4+ effector T cells which have been described in both mice and humans. However, some differences seem to exist between murine and human Th17 cells with regard to their features, origin and role in immunopathology. Murine Th17 cells share their developmental origin with Foxp3+ Treg cells, indeed naive T-cell precursors can be differentiated to regulatory T (Treg) cells by transforming growth factor-β (TGF-β) alone, whereas the contemporaneous presence of TGF-β and IL-6 gives origin to Th17 cells. Human Th17 cells which consistently express the CC chemokine receptor 6 and the equivalent of the murine NK1.1, CD161, appear to exclusively originate in response to IL-1β and IL-23 from a small subset of CD161+CD4+ T-cell precursors detectable in the thymus and in umbilical cord blood. These cells constitutively express the Th17-driving transcription factor retinoic acid-related orphan receptor (ROR){gamma}t and the IL-23R and can also give origin to Th1 cells or Th2 cells under the appropriate polarizing conditions. By contrast, human CD161-naive T cells only give rise to Th1 and Th2 cells, but not Th17 cells. TGF-β may not exert a direct critical role in human Th17 cell differentiation, but indirectly favours their development by inhibiting the development of Th1 cells, which are much more susceptible than Th17 cells to its suppressive activity on cell proliferation. Moreover, while murine Th17 are pathogenic in some murine models of autoimmunity where Th1 cells seem to play a protective role, both Th17 and Th1 certainly contribute to the pathogenesis of human autoimmune and other chronic inflammatory disorders.

Keywords: CD161, IL-1β, IL-23, ROR{gamma}t, TGF-β

Transmitting editor: H. Kikutani

Received 25 July 2008, accepted 28 August 2008.


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