Yuan Huijie, Zhou Shengru, Liu Zhicui, Cong Weiting, Fei Xiaochun, Zeng Weihong, Zhu Haiqin, Xu Renchao, Wang Ying, Zheng Jie, Pan Meng
Department of Dermatology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Invest Dermatol. 2017 Nov;137(11):2362-2370. doi: 10.1016/j.jid.2017.05.032. Epub 2017 Jun 22.
Pemphigus is a skin and mucosal membrane-targeting autoimmune bullous disease. Previous studies have shown that circulating anti-desmoglein1/3 antibodies are pathogenic and mediate blister formation. However, the role of infiltrating immune cells in lesional skin has not been fully investigated. In this study we showed that there existed a large number of B and T lymphocytes and plasma cells in the skin lesions by immunohistochemistry and immunofluorescence staining. In addition, a significantly increased number of Dsg1- and Dsg3-specific B cells could be identified by flow cytometric analysis or enzyme-linked immunospot technique (i.e., ELISPOT) assay. Furthermore, anti-Dsg1 and Dsg3 antibodies could be detected from the supernatant of in vitro cultures with isolated lymphocytes from lesional skin. We found that most T lymphocytes infiltrating pemphigus vulgaris lesions were CD4 T helper cells expressing IL-21 and IL-17a but not typical T follicular helper cells expressing CXCR5. Additionally, our microarray assay showed that the level of chemokine CCL19 was significantly elevated, suggesting active T-/B-lymphocyte trafficking and aggregation in the pemphigus vulgaris lesions. Collectively, our results suggest a critical role of locally infiltrating lymphocytes in pemphigus pathogenesis.
天疱疮是一种以皮肤和黏膜为靶标的自身免疫性大疱性疾病。先前的研究表明，循环中的抗桥粒芯糖蛋白1/3抗体具有致病性并介导水疱形成。然而，浸润性免疫细胞在皮损中的作用尚未得到充分研究。在本研究中，我们通过免疫组织化学和免疫荧光染色显示皮损中存在大量B淋巴细胞、T淋巴细胞和浆细胞。此外，通过流式细胞术分析或酶联免疫斑点技术（即ELISPOT）检测可发现，桥粒芯糖蛋白1和桥粒芯糖蛋白3特异性B细胞数量显著增加。此外，从皮损中分离的淋巴细胞进行体外培养，其培养上清液中可检测到抗桥粒芯糖蛋白1和桥粒芯糖蛋白3抗体。我们发现，浸润寻常型天疱疮皮损的大多数T淋巴细胞是表达白细胞介素21和白细胞介素17a的CD4辅助性T细胞，而非表达CXC趋化因子受体5的典型滤泡辅助性T细胞。此外，我们的微阵列分析显示趋化因子CCL19水平显著升高，提示寻常型天疱疮皮损中存在活跃的T/B淋巴细胞转运和聚集。总体而言，我们的结果表明局部浸润淋巴细胞在天疱疮发病机制中起关键作用。
