Pivotal Role of Dermal IL-17-Producing γδ T Cells in Skin Inflammation

Yihua Cai, Xiaoyan Shen, Chuanlin Ding, Chunjian Qi, Kejia Li, Xia Li, Venkatakrishna R. Jala, Huang ge Zhang, Tian Wang, Jie Zheng, Jun Yan

Research output: Contribution to journalArticle

506 Scopus citations

Abstract

Interleukin-23 (IL-23) and CD4 + T helper 17 (Th17) cells are thought to be critical in psoriasis pathogenesis. Here, we report that IL-23 predominantly stimulated dermal γδ T cells to produce IL-17 that led to disease progression. Dermal γδ T cells constitutively expressed the IL-23 receptor (IL-23R) and transcriptional factor RORγt. IL-17 production from dermal γδ T cells was independent of αβ T cells. The epidermal hyperplasia and inflammation induced by IL-23 were significantly decreased in T cell receptor δ-deficient (Tcrd -/-) and IL-17 receptor-deficient (Il17ra -/-) mice but occurred normally in Tcra -/- mice. Imiquimod-induced skin pathology was also significantly decreased in Tcrd -/- mice. Perhaps further promoting disease progression, IL-23 stimulated dermal γδ T cell expansion. In psoriasis patients, γδ T cells were greatly increased in affected skin and produced large amounts of IL-17. Thus, IL-23-responsive dermal γδ T cells are the major IL-17 producers in the skin and may represent a novel target for the treatment of psoriasis.

Original languageEnglish (US)
Pages (from-to)596-610
Number of pages15
JournalImmunity
Volume35
Issue number4
DOIs
StatePublished - Oct 28 2011

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Cai, Y., Shen, X., Ding, C., Qi, C., Li, K., Li, X., Jala, V. R., Zhang, H. G., Wang, T., Zheng, J., & Yan, J. (2011). Pivotal Role of Dermal IL-17-Producing γδ T Cells in Skin Inflammation. Immunity, 35(4), 596-610. https://doi.org/10.1016/j.immuni.2011.08.001