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

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• 作者：Jong Hoon Kim ; MD^a ; ^b ; Young Joon Choi ; MD^a ; Byung Ha Lee ; PhD^c ; Mi-Young Song ; PhD^d ; Chae Yeon Ban^a ; Jihye Kim ; DVM^a ; Junsik Park ; MD^a ; Song-Ee Kim ; MS^b ; Tae-Gyun Kim ; MD^e ; Su-Hyung Park ; PhD^f ; Hyoung-Pyo Kim ; PhD^e ; Young-Chul Sung ; PhD^c ; ^d ; Soo-Chan Kim ; MD ; PhD^b ; ^{kimsc@yuhs.ac" class="auth_mail" title="E-mail the corresponding author} ; Eui-Cheol Shin ; MD ; PhD^a ; ^{ecshin@kaist.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Psoriasis ; programmed cell death 1 ; programmed cell death ligand 1 ; IL-17A ; T cell
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：137
• 期：5
• 页码：1466-1476.e3
• 全文大小：3363 K

文摘

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^hiVγ4⁻ (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.