Pivotal Role of Lesional and Perilesional T/B Lymphocytes in Pemphigus Pathogenesis
Huijie Yuan, Shengru Zhou, Zhicui Liu, Weiting Cong, Xiaochun Fei, Weihong Zeng, Haiqin Zhu, Renchao Xu, Ying Wang, Jie Zheng, Meng Pan, Huijie Yuan, Shengru Zhou, Zhicui Liu, Weiting Cong, Xiaochun Fei, Weihong Zeng, Haiqin Zhu, Renchao Xu, Ying Wang, Jie Zheng, Meng Pan
Abstract
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.
Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Source: PubMed