The IL-23/IL-17 axis in inflammation
Yoichiro Iwakura, Harumichi Ishigame
Yoichiro Iwakura, Harumichi Ishigame
Published May 1, 2006
Citation Information: J Clin Invest. 2006;116(5):1218-1222. https://doi.org/10.1172/JCI28508.
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Commentary

The IL-23/IL-17 axis in inflammation

Abstract

IL-23 induces the differentiation of naive CD4+ T cells into highly pathogenic helper T cells (Th17/ThIL-17) that produce IL-17, IL-17F, IL-6, and TNF-α, but not IFN-γ and IL-4. Two studies in this issue of the JCI demonstrate that blocking IL-23 or its downstream factors IL-17 and IL-6, but not the IL-12/IFN-γ pathways, can significantly suppress disease development in animal models of inflammatory bowel disease and MS (see the related articles beginning on pages 1310 and 1317). These studies suggest that the IL-23/IL-17 pathway may be a novel therapeutic target for the treatment of chronic inflammatory diseases.

Authors

Yoichiro Iwakura, Harumichi Ishigame

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Figure 1

IL-23 promotes the development of an IL-17–producing CD4+ helper T cell subset.

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IL-23 promotes the development of an IL-17–producing ...
IL-23 induces the differentiation of naive CD4+ T cells into IL-17–producing helper T cells (Th17/ThIL-17) via mechanisms that are distinct from the Th1 and Th2 differentiation pathways. The transcriptional factors critical for the development of Th1 (STAT1, STAT4, and T-bet) and Th2 (STAT6) cells are not required for the induction of Th17/ThIL-17 cells. The transcriptional factor(s) essential for the development of Th17/ThIL-17 cells remain unknown. IFN-γ and IL-4 antagonize each other in the differentiation of Th1 and Th2 cells and the promotion of their function. IFN-γ also suppresses the differentiation of Th17/ThIL-17 cells by reducing IL-23R expression on CD4+ T cells. IL-4 also inhibits the development of Th17/ThIL-17 cells. It is not known, however, whether Th17/ThIL-17 cells inhibit the development of Th1 and Th2 cells. Tregs, an immune-modulating subset of CD4+ T cells, suppress the differentiation and effector function of Th1 and Th2 cells. Recent studies suggest that Treg-derived TGF-β induces the differentiation of Th17/ThIL-17 cells from naive CD4+ T cells in the presence of IL-6 in vitro (26). However, the precise effect(s) of Tregs on Th17/ThIL-17 cells are as yet unknown.