期刊
EXPERIMENTAL NEUROLOGY
卷 312, 期 -, 页码 43-50出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2018.11.006
关键词
Myasthenia gravis; MuSK-myasthenia gravis; Tacrolimus; Th1; Th17; Pathogenic Th17 cells; Follicular T helper cell; Regulatory T helper cell
资金
- Myasthenia Gravis Foundation of America (MGFA)
- National Natural Science Foundation Key International (Regional) Cooperation Research Project [81620108010]
- International Program for Ph.D. Candidates, Sun Yat-sen University
- National Institute of Neurological Disorders and Stroke of the National Institutes of Health [K23NS085049]
Muscle specific tyrosine kinase antibody positive myasthenia gravis (MuSK- MG) is characterized by auto-antibodies against the MuSK protein of the neuromuscular junction resulting in weakness of bulbar and proximal muscles. We previously demonstrated that patients with MuSK-MG have increased pro-inflammatory Th1 and Th17 responses. Tacrolimus, an immunosuppressant used in AChR-MG and transplantation patients, inhibits T cell responses through interference with IL-2 transcription. The therapeutic efficacy and immunological effect of tacrolimus in MuSK-MG is unclear. In the current study we examined the proliferation, phenotype and cytokine production of CD4 + and CD8 + T cells in peripheral blood mononuclear cells of MuSK-MG following a 3-day in vitro culture with or without tacrolimus. We determined that tacrolimus profoundly suppressed CD4 and CD8 T cell proliferation and significantly suppressed Th1 and Th17 responses, as demonstrated by a reduced frequency of IFN-gamma, IL-2, and IL-17 producing CD4 T cells and reduced frequencies of IFN-gamma and IL-2 producing CD8 T cells. Tacrolimus also inhibits pathogenic Th17 cells coproducing IL-17 and IFN-gamma. In addition, tacrolimus suppressed follicular T helper cell (Tfh) and regulatory T helper cell (Treg) subsets. These findings provide preliminary support for tacrolimus as a potential alternative immunosuppressive therapy for MuSK-MG.
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