Osteopontin exacerbates the progression of experimental autoimmune myasthenia gravis by affecting the differentiation of T cell subsets

Jiarui Zhao; Jia Jing; Wei Zhao; Xinrong Li; Lixuan Hou; Chunfeng Zheng; Qingfei Kong; Wenjin Li; Xiuhua Yao; Lulu Chang; Hulun Li; Lili Mu; Guangyou Wang; Jinghua Wang

doi:10.1016/j.intimp.2020.106335

Osteopontin exacerbates the progression of experimental autoimmune myasthenia gravis by affecting the differentiation of T cell subsets

Int Immunopharmacol. 2020 Feb 25:82:106335. doi: 10.1016/j.intimp.2020.106335. Online ahead of print.

Authors

Jiarui Zhao¹, Jia Jing¹, Wei Zhao¹, Xinrong Li¹, Lixuan Hou¹, Chunfeng Zheng², Qingfei Kong¹, Wenjin Li¹, Xiuhua Yao³, Lulu Chang¹, Hulun Li⁴, Lili Mu⁵, Guangyou Wang⁶, Jinghua Wang⁷

Affiliations

¹ Department of Neurobiology, Harbin Medical University, Heilongjiang Provincial Key Laboratory of Neurobiology, Harbin, Heilongjiang 150086, China.
² The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar City, Heilongjiang 161000, China.
³ Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, Tianjin Huanhu Hospital, Tianjin 300350, China.
⁴ Department of Neurobiology, Harbin Medical University, Heilongjiang Provincial Key Laboratory of Neurobiology, Harbin, Heilongjiang 150086, China; Ministry of Education Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China, Harbin Medical University, Harbin, Heilongjiang 150086, China.
⁵ Department of Neurobiology, Harbin Medical University, Heilongjiang Provincial Key Laboratory of Neurobiology, Harbin, Heilongjiang 150086, China; Ministry of Education Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China, Harbin Medical University, Harbin, Heilongjiang 150086, China. Electronic address: mulili@ems.hrbmu.edu.cn.
⁶ Department of Neurobiology, Harbin Medical University, Heilongjiang Provincial Key Laboratory of Neurobiology, Harbin, Heilongjiang 150086, China. Electronic address: wangguangyou@hrbmu.edu.cn.
⁷ Department of Neurobiology, Harbin Medical University, Heilongjiang Provincial Key Laboratory of Neurobiology, Harbin, Heilongjiang 150086, China. Electronic address: wangjinghua@ems.hrbmu.edu.cn.

PMID: 32109680
DOI: 10.1016/j.intimp.2020.106335

Abstract

Osteopontin (OPN) is a multifunctional extracellular matrix phosphoprotein that has a specific and complicated structure, and contributes to numerous physiological and pathological activities. The mechanism of OPN in many diseases has been confirmed; however, the role of OPN in myasthenia gravis (MG) remains unclear. In this study, we recombined rat OPN protein in vitro, and assessed how OPN affects the development of autoimmunity using an experimental autoimmune myasthenia gravis (EAMG) rat model. The results showed that the concentration of OPN in serum was up-regulated. Both mRNA and protein levels in splenocytes increased in the EAMG model. OPN treatment in vitro strongly promoted the differentiation of Th1 cells, and inhibited the differentiation of Treg cells. Intraperitoneal injection of OPN revealed the early incidence of EAMG, and more serious disease. This effect was accompanied by an increased percentage of Th1 cells. In conclusion, OPN likely exacerbates the pathogenesis of EAMG by promoting the differentiation of Th1 cells and inhibiting the differentiation of Treg cells.

Keywords: Autoimmune disease; B cells; Experimental autoimmune myasthenia gravis; Osteopontin; T helper cells.