Programmed cell death ligand 1 alleviates psoriatic inflammation by suppressing IL-17A production from programmed cell death 1-high T cells

Jong Hoon Kim, Young Joon Choi, Byung Ha Lee, Mi Young Song, Chae Yeon Ban, Jihye Kim, Junsik Park, Song Ee Kim, Tae Gyun Kim, Su Hyung Park, Hyoung Pyo Kim, Young Chul Sung, Soo Chan Kim, Eui Cheol Shin

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Abstract

Background Psoriasis is one of the most common chronic inflammatory diseases of the skin. Recently, IL-17-producing T cells have been shown to play a critical role in psoriatic inflammation. Programmed cell death 1 (PD-1) is a coinhibitory receptor expressed on T cells in various chronic inflammatory diseases; however, the expression and function of PD-1 during psoriatic inflammation have not previously been characterized. Objective We examined PD-1 expression on IL-17A-producing T cells from imiquimod-treated mice and patients with psoriasis. Additionally, we investigated the therapeutic effect of recombinant programmed cell death ligand 1 (PD-L1) protein on imiquimod-induced psoriatic inflammation. Methods PD-1 expression on IL-17A-producing γδ T cells from imiquimod-treated mice was examined by means of multicolor flow cytometric analysis. In the psoriatic skin of patients, PD-1 and IL-17A expression was analyzed by using immunofluorescence. The therapeutic effect of PD-L1-Fc fusion protein (PD-L1-Fc) was assessed in imiquimod-treated mice ex vivo and in vivo. Results During imiquimod-induced psoriatic inflammation, PD-1 is overexpressed on CD27-Vγ1- γδ T cells. Furthermore, PD-1 expression on IL-17A+ T cells was confirmed in psoriatic skin tissues from patients and imiquimod-treated mice. In the CD27-Vγ1- γδ T-cell population, Vγ4- γδ T cells with Vγ6 mRNA expression showed a high level of PD-1 expression. Furthermore, these PD-1hiVγ4- (Vγ6+) γδ T cells were specialized for anti-CD3-induced IL-17A production, which was inhibited by PD-L1-Fc treatment. In imiquimod-treated mice PD-L1-Fc reduced psoriatic inflammation when given alone and enhanced the therapeutic effect of anti-p40 when given in combination. Conclusion PD-1 is overexpressed in IL-17A-producing T cells in both imiquimod-treated mice and patients with psoriasis. Moreover, recombinant PD-L1-Fc alleviates psoriatic inflammation in imiquimod-treated mice.

Original languageEnglish
Pages (from-to)1466-1476.e3
JournalJournal of Allergy and Clinical Immunology
Volume137
Issue number5
DOIs
Publication statusPublished - 2016 May 1

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Kim, J. H., Choi, Y. J., Lee, B. H., Song, M. Y., Ban, C. Y., Kim, J., Park, J., Kim, S. E., Kim, T. G., Park, S. H., Kim, H. P., Sung, Y. C., Kim, S. C., & Shin, E. C. (2016). Programmed cell death ligand 1 alleviates psoriatic inflammation by suppressing IL-17A production from programmed cell death 1-high T cells. Journal of Allergy and Clinical Immunology, 137(5), 1466-1476.e3. https://doi.org/10.1016/j.jaci.2015.11.021