Negative regulation of dendritic cell activation in psoriasis mediated via CD100-plexin-B2
Negative regulation of dendritic cell activation in psoriasis mediated via CD100-plexin-B2
复制标题
CD100-plexin-B2 介导的银屑病树突状细胞活化的负调节
DOI：
10.1002/path.5383
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发表时间：
2020-02-21
影响因子：
7.3
通讯作者：
Li，Wei
中科院分区：
文献类型：
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作者：
Xiao，Chunying;Luo，Yang;Li，Wei
银屑病是一种慢性炎症性皮肤病，其中树突状细胞 (DC) 通过诱导 Th1/Th17 免疫反应发挥着关键作用；然而，银屑病中 DC 激活的调节仍然很大程度上未知。此前我们发现银屑病患者血清中可溶性CD100水平升高，CD100促进角质形成细胞内炎症小体的活化。在本研究中，CD100基因敲除小鼠被用来产生咪喹莫特（IMQ）诱导的银屑病皮炎，结果是，与野生型对照相比，银屑病皮炎早期而非晚期的皮肤炎症明显加剧。这主要归因于造血细胞中CD100的缺乏。来自 CD100 敲除小鼠的骨髓来源的 DC，而非 T 细胞或角质形成细胞，在 IMQ 以 plexin-B2 依赖性方式刺激后，产生显着增加的 IL-1β、IL-36 和 IL-23 水平。此外，银屑病患者 DC 上的 plexin-B2 表面水平低于健康个体，并且 CD100 减弱了 IMQ 诱导的银屑病患者单核细胞来源的 DC 中 IL-1β 和 IL-36 的产生。我们的结果揭示了银屑病中 DC 激活的负调节机制，该机制是通过 CD100-plexin-B2 以细胞类型和受体特异性方式介导的。 © 2020 大不列颠及爱尔兰病理学会。由约翰·威利父子有限公司出版
Psoriasis is a chronic inflammatory skin disease in which dendritic cells (DCs) play a pivotal role by inducing Th1/Th17 immune responses; however, the regulation of DC activation in psoriasis remains largely unknown. Previously we found that the level of soluble CD100 was increased in sera of psoriasis patients, and CD100 promoted the activation of inflammasome in keratinocytes. In the present study, CD100 knockout mice were utilized for generation of imiquimod (IMQ)‐induced psoriatic dermatitis, with the result that skin inflammation in the early, but not late, phase of the psoriatic dermatitis was significantly exacerbated compared to that in wild‐type controls. This was attributed mainly to the deficiency of CD100 in hematopoietic cells. Bone marrow‐derived DCs, but not T cells or keratinocytes, from CD100 knockout mice produced significantly increased levels of IL‐1β, IL‐36, and IL‐23 upon stimulation with IMQ in a plexin‐B2‐dependent manner. Moreover, the surface level of plexin‐B2 on DCs of psoriasis patients was lower than that of healthy individuals, and CD100 attenuated IMQ‐induced production of IL‐1β and IL‐36 from monocyte‐derived DCs of psoriasis patients. Our results uncovered a negative regulatory mechanism for DCs activation in psoriasis, which was mediated via CD100–plexin‐B2 in a cell type‐ and receptor‐specific manner. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.