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Clin Immunol. 2019 Jun;203:142-153. doi: 10.1016/j.clim.2019.05.006. Epub 2019 May 9.

Inhibition of ROCK activity regulates the balance of Th1, Th17 and Treg cells in myasthenia gravis.

Author information

1
Department of Neurology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China.
2
Department of Neurology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China. Electronic address: zhao_chongbo@fudan.edu.cn.

Abstract

Aberrant ROCK activation has been found in patients with several autoimmune diseases, but the role of ROCK in myasthenia gravis (MG) has not yet been clearly investigated. Here, we demonstrated that ROCK activity was significantly higher in peripheral blood mononuclear cells (PBMCs) from MG patients. ROCK inhibitor Fasudil down-regulated the proportions of Th1 and Th17 cells in PBMCs of MG patients in vitro. Intraperitoneal injection of Fasudil ameliorated the severity of experimental autoimmune myasthenia gravis (EAMG) rats and restored the balance of Th1/Th2/Th17/Treg subsets. Furthermore, Fasudil inhibited the proliferation of antigen-specific Th1 and Th17 cells, and inhibited CD4 + T cells differentiated into Th1 and Th17 through decreasing phosphorylated Stat1 and Stat3, but promoted Treg cell differentiation through increasing phosphorylated Stat5. We conclude that dysregulated ROCK activity may be involved in the pathogenic immune response of MG and inhibition of ROCK activity might serve as a novel treatment strategy for MG.

KEYWORDS:

Fasudil; Myasthenia gravis; Rho kinase; T helper cells

PMID:
31078707
DOI:
10.1016/j.clim.2019.05.006

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