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J. Allergy Clin. Immunol., Available online 27 January 2016 | doi:10.1016/j.jaci.2015.11.021 Programmed cell death ligand 1 alleviates psoriatic inflammation by suppressing IL-17A production from programmed cell death 1–high T cells

Abstract

Jong Hoon Kim, MD^{a, b}, Young Joon Choi, MD^a, Byung Ha Lee, PhD^c, Mi-Young Song, PhD^d, Chae Yeon Ban^a, Jihye Kim, DVM^a, Junsik Park, MD^a, Song-Ee Kim, MS^b, Tae-Gyun Kim, MD^e, Su-Hyung Park, PhD^f, Hyoung-Pyo Kim, PhD^e, Young-Chul Sung, PhD^{c, d}, Soo-Chan Kim, MD, PhD^b,*, Eui-Cheol Shin, MD, PhD^a,*

^a Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea

^f Laboratory of Translational Immunology and Vaccinology, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea

^b Department of Dermatology and Cutaneous Biology Research Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

^e Department of Environmental Medical Biology, Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul, Korea

^c Genexine, Seongnam, Korea

^d Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea

^*Corresponding authors

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-1^hiVγ4^- (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.

Key words : Psoriasis; programmed cell death 1; programmed cell death ligand 1; IL-17A; T cell

논문정보

형식Research article
게재일2016년 01월 (BRIC 등록일 2016-02-01)
연구진국내 연구진
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