Oncotarget

Research Papers:

Regulatory effects of Nr4a2 on Th2 cells from patients with pemphigus vulgaris

Jianbo Chen, Yao Zhang, Yunsheng Liang, Ming Zhao, Hai Long, Rong Xiao, Haijing Wu, Jieyue Liao, Shuaihantian Luo, Guiying Zhang _ and Qianjin Lu

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Oncotarget. 2018; 9:11258-11267. https://doi.org/10.18632/oncotarget.24371

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Abstract

Jianbo Chen1,*, Yao Zhang1,*, Yunsheng Liang1, Ming Zhao1, Hai Long1, Rong Xiao1, Haijing Wu1, Jieyue Liao1, Shuaihantian Luo1, Guiying Zhang1 and Qianjin Lu1

1Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, Changsha 410011, China

*These authors have contributed equally to this work

Correspondence to:

Guiying Zhang, email: lindazgy@csu.edu.cn

Qianjin Lu, email: qianlu5860@csu.edu.cn

Keywords: cytokines; negative regulation; Nr4a2; pemphigus vulgaris; Th2 cells

Received: July 13, 2017     Accepted: December 03, 2017     Published: February 01, 2018

ABSTRACT

Pemphigus vulgaris is an autoimmune blistering disease characterized by a loss of epidermal cell–cell adhesion caused by anti-desmoglein (Dsg) autoantibodies. The pathogenesis of PV remains unclear. However, abnormal frequency and function of Th2 cells are believed to contribute to PV. We investigated Nr4a2, a transcription factor, which has been found to regulate T cell differentiation, for its association with Th2 cell differentiation and functions in PV. We found significantly decreased mRNA and protein levels of Nr4a2 in CD4+ T cells from patients with PV, compared with healthy control subjects. In addition, mRNA and protein levels of Nr4a2 in CD4+ T cells were inversely correlated with serum levels of IL-4 and IL-13 in patients with PV. Overexpression of Nr4a2 in CD4+ T cells from patients with PV significantly reduced the mRNA levels of GATA3, IL-4, and IL-13, while Nr4a2 siRNA treatment showed the reverse effects on the expression of these Th2-related cytokines and transcription factors. The data suggest that the altered level of Nr4a2 in CD4+ T cells is associated with the development of PV. Nr4a2 may contribute to the pathogenesis of PV by negatively regulating Th2 activity and secretion of Th2-related cytokines.


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