The Role of PD-L1 on Langerhans Cells in the Regulation of Psoriasis
The Role of PD-L1 on Langerhans Cells in the Regulation of Psoriasis
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DOI：
10.1016/j.jid.2022.06.006
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发表时间：
2022-11-18
影响因子：
6.5
通讯作者：
Okiyama, Naoko
中科院分区：
文献类型：
--
作者：
Tanaka, Ryota;Ichimura, Yuki;Okiyama, Naoko
朗格汉斯细胞（LC）是具有有效抗原呈递细胞能力的皮肤驻留细胞，据报道其在银屑病的发展中发挥一定作用，银屑病是一种由IL-17 A产生细胞、T辅助细胞17和TCR-γ δ（低）T细胞介导的炎性皮肤病。银屑病皮损中的LC而非正常皮肤中的LC表达PD-L1，PD-L1与PD-1（一种免疫检查点分子）结合，以负调节免疫反应。本研究的目的是阐明LC通过PD-1/PD-L1轴在咪喹莫特诱导的银屑病样皮炎小鼠模型中的调节作用。在野生型C57 BL/6）小鼠上应用咪喹莫特诱导了耳皮肤和皮肤引流淋巴结中LC上的PD-L1表达。为了进一步鉴定LC上表达的PD-L1的功能作用，我们产生了LC上缺乏PD-L1表达的条件性敲除小鼠（Pd-l1-cKO小鼠）。Pd-l1-cKO小鼠表现出比其对照同窝小鼠显著更严重的咪喹莫特诱导的银屑病样皮炎。流式细胞术分析显示，与对照同窝小鼠相比，在应用咪喹莫特的Pd-l1-cKO小鼠中，耳部皮肤样品中活化的产生IL-17 A的γ δ（低）T细胞的频率增加，并且皮肤引流淋巴结中CCR 6（+）迁移的γ δ（低）T细胞产生的IL-17 A增加。总的来说，LC通过PD-L1破坏银屑病的恶化。
Langerhans cells (LCs) are skin-resident cells with potent antigen-presenting cell capabilities, which reportedly play some roles in the development of psoriasis, an inflammatory skin disease mediated by IL-17A-producing cells, T helper 17 cells, and TCR-gamma delta(low) T cells. LCs in psoriatic skin lesions but not in normal skin express PD-L1, which binds to PD-1, an immune checkpoint molecule, to negatively regulate immune reactions. The aim of this study is to elucidate the regulatory role of LCs through the PD-1/PD-L1 axis in a murine model of imiquimodinduced psoriasis-like dermatitis. Imiquimod application on wild-type C57BL/6) mice induced PD-L1 expression on LCs both in the ear skin and skin-draining lymph nodes. To further identify the functional role of PD-L1 expressed on LCs, we generated conditional knockout mice lacking PD-L1 expression on LCs (Pd-l1-cKO mice). Pd-l1-cKO mice presented significantly more severe imiquimod-induced psoriasis-like dermatitis than their control littermates. Flow cytometric analysis showed that the frequency of activated IL-17A-producing gamma delta(low) T cells was increased in the ear skin samples, and IL-17A production by CCR6(+) migrating gamma delta(low) T cells increased in the skin-draining lymph nodes in imiquimod-applied Pd-l1-cKO mice than in control littermates. Collectively, LCs disrupt the exacerbation of psoriasis through PD-L1.