CD100-Plexin-B1/B2介导γδT细胞-角质形成细胞相互作用参与银屑病发病及机制研究

Proliferation of keratinocytes (KC) and inflammatory infiltration of T cells are two key features of psoriasis, and crosstalk of the above two factors is very important for the pathogenesis of psoriasis. However, the interaction between KC and T cells are not clear yet. Most recently, it is reported that plexin-B2 was expressed on the surface of mouse KC, promoting the recovery of skin trauma by stimulating the morphology changes and migration of γδ T cells expressing CD100. Our preliminary data showed that there was greatly increased level of soluble CD100 in the sera of psoriasis patients, and plexin-B1and B2 was expressed in the epidermis of psoriasis patients, while plexin-B1/2 was not found in normal epidermis, indicating that CD100-Plexin-B1/2 induced interaction between KC and T cells might participate in the pathogenesis of psoriasis. In the present study, we are planning to study the role of CD100-plexin-B1/2 interaction in the psoriasis patient and mice model. Our study may contribute to elucidating the pathogenesis of psoriasis and may lead to the finding of new therapeutic target for psoariasis.

角质形成细胞(KC)过度增生和T细胞为主的炎细胞浸润是银屑病的基本病理特征，二者相互作用是银屑病发生发展的关键机制。然而，KC-T细胞相互作用的方式及机制尚未完全阐明。最近研究发现小鼠KC表面表达Plexin-B2，与γδT细胞表面CD100结合后促进γδT细胞形态改变和迁徙，参与皮肤创伤修复。本研究组发现银屑病患者血清可溶性CD100水平显著增高，Plexin-B1和B2高水平表达于银屑病皮损KC，提示CD100-Plexin-B1/B2很可能介导KC-T细胞相互作用而参与银屑病发病。本研究拟在银屑病患者和咪喹莫特小鼠银屑病模型水平阐明CD100和Plexin-B1/B2相互作用在银屑病发病中的作用，为揭示CD100-Plexin-B1/B2介导γδ T细胞-KC相互作用参与银屑病发病及其机制进行积极的探索，为寻找银屑病治疗的新靶点提供有益的思路。

角质形成细胞(KC)过度增生和T细胞为主的炎细胞浸润是银屑病的基本病理特征，二者相互作用是银屑病发生发展的关键机制。然而，KC-T细胞相互作用的方式及机制尚未完全阐明。最近研究发现小鼠KC表面表达Plexin-B2，与γδT细胞表面CD100结合后促进γδT细胞形态改变和迁徙，参与皮肤创伤修复。本研究组发现银屑病患者血清可溶性CD100水平显著增高，Plexin-B1和B2高水平表达于银屑病皮损KC，提示CD100-Plexin-B1/B2很可能介导KC-T细胞相互作用而参与银屑病发病。在以往工作基础上，本研究组分析了Plexin-B2和CD100在银屑病皮损和咪喹莫特小鼠银屑病模型中的表达，体外和体内实验分别研究了CD100\Plexin-B2相互作用对于角质形成细胞和咪喹莫特银屑病模型的影响。结果显示，Plexin-B2的表达在银屑病患者皮损和咪喹莫特银屑病模型都增高，银屑病患者血清中可溶型CD100水平增高。体外研究发现可溶性CD100促进角质形成细胞的增殖和迁移，Plexin-B2-siRNA可以抑制这一作用。给予咪喹莫特银屑病小鼠模型皮肤外用Plexin-B2-siRNA可以抑制皮炎的进展，指标包括表皮厚度、真皮炎症浸润以及细胞因子分泌。有意思的是，银屑病模型表皮内γδT细胞的浸润在应用Plexin-B2-siRNA后显著降低，提示Plexin-B2在角质形成细胞表达降低后可能阻断真皮γδT细胞向表皮的迁移，这一点对于银屑病的发病机制非常重要。Plexin-B2基因沉默还可以抑制体外培养条件下角质形成细胞表达IL-36, CXCL1 and CCL20。Plexin-B2的下游信号分子机制包括Erk和Akt的磷酸化。我们的研究首次揭示了CD100\Plexin-B2相互作用在银屑病发病机制中的作用，提示Plexin-B2可能作为治疗银屑病的潜在靶点。