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-1hiVγ4- (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.
Bibliographical notePublisher Copyright:
© 2016 American Academy of Allergy, Asthma & Immunology.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy