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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 
 Journal of Allergy and Clinical Immunology, Vol.137(5) : 1466-1476, 2016 
Journal Title
 Journal of Allergy and Clinical Immunology 
Issue Date
Adjuvants, Immunologic ; Aminoquinolines ; Animals ; B7-H1 Antigen/pharmacology ; B7-H1 Antigen/therapeutic use ; Humans ; Inflammation/metabolism ; Interleukin-17/metabolism* ; Mice, Inbred C57BL ; Programmed Cell Death 1 Receptor/metabolism* ; Psoriasis/chemically induced ; Psoriasis/drug therapy ; Psoriasis/metabolism* ; Recombinant Proteins/pharmacology ; Recombinant Proteins/therapeutic use ; Skin/drug effects ; Skin/metabolism ; T-Lymphocyte Subsets/metabolism*
IL-17A ; Psoriasis ; T cell ; programmed cell death 1 ; programmed cell death ligand 1
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(hi)Vγ4(-) (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.
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1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Environmental Medical Biology (환경의생물학교실) > 1. Journal Papers
Yonsei Authors
김송이(Kim, Song Ee)
김수찬(Kim, Soo Chan) ORCID logo https://orcid.org/0000-0002-2327-4755
김종훈(Kim, Jong Hoon) ORCID logo https://orcid.org/0000-0002-3385-8180
김형표(Kim, Hyoung Pyo) ORCID logo https://orcid.org/0000-0003-1441-8822
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