IL-17-producing cells go it alone

Honey, Karen

doi:10.1038/nri1737

Research Highlight
Published: 20 October 2005

Cytokines

IL-17-producing cells go it alone

Karen Honey

Nature Reviews Immunology volume 5, page 829 (2005)Cite this article

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IL-23-dependent, IL-17-producing CD4⁺ T cells are associated with autoimmunity. However, it is not clear whether these cells differentiate along a pathway that is distinct from those pathways that give rise to T_H1 and T_H2 cells or whether they are derived from a T_H1-cell intermediate. Both groups set out to address this issue and found that, when naive CD4⁺ T cells were stimulated in vitro through their T-cell receptor (TCR) in the presence of IL-23, few cells produced IL-17, but a substantial proportion produced interferon-γ (IFN-γ). However, if IFN-γ-specific antibody was also included in the culture then a large population of IL-17-producing cells emerged. A further increase in the proportion of IL-17-producing CD4⁺ T cells was observed if IL-4-specific antibody was also added to the culture, indicating that IFN-γ and IL-4 independently inhibit the generation of IL-17-producing cells.

Harrington et al. further investigated the factors that are required for the development of IL-17-producing cells in vitro. They found that naive CD4⁺ T cells isolated from mice that were deficient in signal transducer and activator of transcription 1 (STAT1), STAT4 or T-bet (factors that are required for differentiation into T_H1 cells) were not impaired in their ability to differentiate into IL-17-producing cells when stimulated through their TCR in the presence of IL-23. Similarly, the development of IL-17-producing cells was not impaired when the stimulated naive CD4⁺ T cells were isolated from mice that were deficient in STAT6, which promotes differentiation into T_H2 cells.

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ORIGINAL RESEARCH PAPERS

Harrington, L. E. et al. Interleukin 17-producing CD4⁺ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nature Immunol. 6, 1123–1132 (2005)
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Park, H. et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nature Immunol. 6, 1133–1141 (2005)
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