Ibudilast Inhibits Th17 Cell Differentiation from Naïve Human T Cells

DOI 機関リポジトリ Web Site

この論文をさがす

抄録

type:TOHO University Scholarly Publication

Original Article

Background: T helper cells that secrete interleukin (IL)-17 (Th17 cells) are important in the pathogenesis of autoimmune diseases such as multiple sclerosis (MS). In addition, Th17 cells are associated with secondary inflammation induced by cerebral infarction. The nonselective phosphodiesterase inhibitor ibudilast ameliorates inflammation and neurodegeneration in patients with ischemic stroke and MS and is used in Japan to treat bronchial asthma and cerebrovascular disorders. Several reports have shown that ibudilast decreases production of tumor necrosis factor α, IL-1β, IL-6, and interferon-γ and suppresses differentiation of T helper 1 (Th1) cells. However, it is not clear if ibudilast suppresses Th17 differentiation and IL-17 production. Thus, we investigated if ibudilast inhibits differentiation of human Th17 cells. Methods: Naïve T cells were isolated from 5 healthy volunteers, using a magnetic beads kit. Differentiation of Th17 cells was then stimulated in vitro using treatments with anti-CD3, anti-CD28, IL-1β, IL-6, IL-21, IL-23, and transforming growth factor-beta1 (TGF-β1), with or without ibudilast, for 1 week. Populations of Th17 cells were measured using flow cytometry with anti-IL-17 antibodies. The activity of signal transducer and activator of transcription 3 (STAT3) was analyzed in naïve T cells, using enzyme-linked immunosorbent assays after stimulation with the above cytokines for 30 min. Results: Th17 cell differentiation was significantly inhibited by ibudilast. Conclusions: Ibudilast inhibits Th17 cell differentiation and may contribute to development of new treatments for MS.

収録刊行物

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ