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

卷:137

Article

Kim, Jong Hoon^1,3,4  Choi, Young Joon¹  Lee, Byung Ha⁶  Song, Mi-Young⁷  Ban, Chae Yeon¹  Kim, Jihye¹  Park, Junsik¹  Kim, Song-Ee^3,4  Kim, Tae-Gyun⁵  Park, Su-Hyung²  Kim, Hyoung-Pyo⁵  Sung, Young-Chul⁶  Kim, Soo-Chan^3,4  Shin, Eui-Cheol¹ 

[1] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Lab Immunol & Infect Dis, 291 Daehak Ro, Taejon 305701, South Korea

[2] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Lab Translat Immunol & Vaccinol, Taejon 305701, South Korea

[3] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Dermatol, 211 Eonjuro, Seoul 135720, South Korea

[4] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Cutaneous Biol Res Inst, Seoul 135720, South Korea

[5] Yonsei Univ, Coll Med, Inst Trop Med, Dept Environm Med Biol, Seoul 135720, South Korea

[6] Genexine, Songnam, South Korea

[7] Pohang Univ Sci & Technol, Div Integrat Biosci & Biotechnol, Pohang, South Korea

关键词: Psoriasis;    programmed cell death 1;    programmed cell death ligand 1;    IL-17A;    T cell;   

DOI  :  10.1016/j.jaci.2015.11.021

来源: Elsevier

【 摘 要 】

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 gamma delta 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(-)V gamma 1(-) gamma delta 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(-)V gamma 1(-) gamma delta T-cell population, V gamma 4(-) gamma delta T cells with V gamma 6 mRNA expression showed a high level of PD-1 expression. Furthermore, these PD-1(hi)V gamma 4(-)(V gamma 6(+)) gamma delta Tcells 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.

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