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

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-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.

• Authors: 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: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 137 Issue 5 Pg. 1466-1476.e3 (05 2016) ISSN: 1097-6825 [Electronic] United States
• PMID: 26824999 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Adjuvants, Immunologic
• Aminoquinolines
• B7-H1 Antigen
• IL17A protein, human
• Interleukin-17
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor
• Recombinant Proteins
• Imiquimod

Topics

• Adjuvants, Immunologic
• Aminoquinolines
• Animals
• B7-H1 Antigen (pharmacology, therapeutic use)
• Humans
• Imiquimod
• Inflammation (metabolism)
• Interleukin-17 (metabolism)
• Mice, Inbred C57BL
• Programmed Cell Death 1 Receptor (metabolism)
• Psoriasis (chemically induced, drug therapy, metabolism)
• Recombinant Proteins (pharmacology, therapeutic use)
• Skin (drug effects, metabolism)
• T-Lymphocyte Subsets (metabolism)