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

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 inflammator...

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Published in:Journal of allergy and clinical immunology 2016-05, Vol.137 (5), p.1466-1476.e3
Main Authors: Kim, Jong Hoon, MD, Choi, Young Joon, MD, Lee, Byung Ha, PhD, Song, Mi-Young, PhD, Ban, Chae Yeon, Kim, Jihye, DVM, Park, Junsik, MD, Kim, Song-Ee, MS, Kim, Tae-Gyun, MD, Park, Su-Hyung, PhD, Kim, Hyoung-Pyo, PhD, Sung, Young-Chul, PhD, Kim, Soo-Chan, MD, PhD, Shin, Eui-Cheol, MD, PhD
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic
Allergy and Immunology
Aminoquinolines
Animals
Apoptosis
B7-H1 Antigen - pharmacology
B7-H1 Antigen - therapeutic use
Cell death
Humans
IL-17A
Inflammation
Inflammation - metabolism
Interleukin-17 - metabolism
Ligands
Lymphocytes
Mice, Inbred C57BL
Pathogenesis
programmed cell death 1
Programmed Cell Death 1 Receptor - metabolism
programmed cell death ligand 1
Proteins
Psoriasis
Psoriasis - chemically induced
Psoriasis - drug therapy
Psoriasis - metabolism
Recombinant Proteins - pharmacology
Recombinant Proteins - therapeutic use
Rodents
Skin - drug effects
Skin - metabolism
T-Lymphocyte Subsets - metabolism
T cell
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Summary: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-1hi 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.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2015.11.021