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

2008, International Immunology

T helper 17 (T h 17) cells represent a new subset of CD41 effector T cells which have been described in both mice and humans. However, some differences seem to exist between murine and human T h 17 cells with regard to their features, origin and role in immunopathology. Murine T h 17 cells share their developmental origin with Foxp31 Treg cells, indeed naive T-cell precursors can be differentiated to regulatory T (Treg) cells by transforming growth factor-b (TGF-b) alone, whereas the contemporaneous presence of TGF-b and IL-6 gives origin to T h 17 cells. Human T h 17 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-1b and IL-23 from a small subset of CD1611CD41 T-cell precursors detectable in the thymus and in umbilical cord blood. These cells constitutively express the T h 17-driving transcription factor retinoic acid-related orphan receptor (ROR)gt and the IL-23R and can also give origin to T h 1 cells or T h 2 cells under the appropriate polarizing conditions. By contrast, human CD161-naive T cells only give rise to T h 1 and T h 2 cells, but not T h 17 cells. TGF-b may not exert a direct critical role in human T h 17 cell differentiation, but indirectly favours their development by inhibiting the development of T h 1 cells, which are much more susceptible than T h 17 cells to its suppressive activity on cell proliferation. Moreover, while murine T h 17 are pathogenic in some murine models of autoimmunity where T h 1 cells seem to play a protective role, both T h 17 and T h 1 certainly contribute to the pathogenesis of human autoimmune and other chronic inflammatory disorders.

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