Interferon regulatory factor 1 enhances T cell differentiation in patients with myasthenia gravis

Interferon regulatory factor 1 is involved in many autoimmune conditions and is increased in patients with myasthenia gravis. However, its function in myasthenia gravis remains unclear. Herein, we explored the function of interferon regulatory factor 1 in myasthenia gravis, with an aim to understand the underlying mechanisms. Patients with myasthenia gravis who had acetylcholine receptor antibodies were included in the study. Peripheral blood lymphocytes were extracted from the included patients, and B lymphocyte subsets were isolated. Next, T and B cells from peripheral blood were co-cultured to explore the interferon regulatory factor 1-related mechanisms in myasthenia gravis. Chromatin immunoprecipitation experiments confirmed an interaction between interferon regulatory factor 1 and the CD180 promoter region. Dual-luciferase reporter gene confirmed the transcriptional activity of interferon regulatory factor 1 on CD180 promoter. In vitro results further indicated that interferon regulatory factor 1 promoted B cell activation and T cell differentiation via the inhibition of CD180. Interferon regulatory factor 1 recruited histone deacetylase 1 to inhibit CD180 transcription. Additionally, histone deacetylase 1 promoted B cell activation and T cell differentiation. Finally, in vitro experiments demonstrated that CD180 inhibited B cell activation and T cell differentiation by inhibiting the Toll-like Receptor 4/mitogen-activated protein kinases/nuclear factor-kappa B pathway. Collectively, our results suggest that interferon regulatory factor 1 enhances T cell differentiation by recruiting histone deacetylase 1 to block B cell CD180 transcription in myasthenia gravis via the Toll-like Receptor 4/mitogenactivated protein kinases/nuclear factor-kappa B pathway. Together, these findings indicate the important role of interferon regulatory factor 1 in myasthenia gravis and suggest its molecular mechanisms. They also provide new ideas and targets for diagnosing and treating myasthenia gravis, which will be both scientifically and clinically valuable.

B cell; CD180; T cell; Toll-like receptor 4; autoimmune condition; histone deacetylase 1; interferon regulatory factor 1; mitogen-activated protein kinase; myasthenia gravis; nuclear factor-kappa B.