Pivotal Role of Lesional and Perilesional T/B Lymphocytes in Pemphigus Pathogenesis.

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.

• Authors: Huijie Yuan, Shengru Zhou, Zhicui Liu, Weiting Cong, Xiaochun Fei, Weihong Zeng, Haiqin Zhu, Renchao Xu, Ying Wang, Jie Zheng, Meng Pan
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 137 Issue 11 Pg. 2362-2370 (11 2017) ISSN: 1523-1747 [Electronic] United States
• PMID: 28647348 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Desmoglein 1
• Interleukin-17
• Interleukins
• interleukin-21

Topics

• B-Lymphocytes (immunology, metabolism)
• Biopsy, Needle
• Blotting, Western
• Case-Control Studies
• Cell Movement (immunology)
• Desmoglein 1 (immunology, metabolism)
• Enzyme-Linked Immunosorbent Assay (methods)
• Enzyme-Linked Immunospot Assay
• Female
• Humans
• Immunohistochemistry
• Interleukin-17 (metabolism)
• Interleukins (metabolism)
• Male
• Pemphigus (immunology, pathology)
• Reference Values
• Role
• T-Lymphocytes (immunology, metabolism)