フジイ　チヒロ   FUJII CHIHIRO   藤井　ちひろ    所属   関西医科大学  神経内科学講座    職種   講師
言語種別	英語
発表タイトル	Increased IL-21 production by follicular helper T cells in myasthenia gravis
会議名	第60回日本神経学会学術大会
学会区分	全国規模の学会
発表形式	ポスター掲示
講演区分	一般
発表者・共同発表者	◎Ashida S, Fujii C, Okada Y, Hashi Y, Hamatani M, Nishigori, R Ochi H, Kawamura K, Nokihara K, Takahashi R, Mizuno T, Kondo T.
発表年月日	2019/05/24
開催地 （都市, 国名）	大阪
概要	[Introduction] Anti-acetylcholine receptor antibody is produced with help for C-X-Chemokine Receptor 5 (CXCR5)-positive follicular helper T cells (Tfh) in myasthenia gravis (MG). CXCR5, which is also expressed on B cells, is important for their homing to lymphoid organs. We previously reported that the frequency of activated Tfh which highly express Inducible Costimulator (ICOS) (ICOShigh Tfh) is elevated in MG, which is corrected by immunotherapy. Here, we analyzed the production of Interleukin (IL)-21 by Tfh in MG and healthy controls (HC), and the effect of IL-21 on B and Tfh cell.[Methods] We isolated Tfh from peripheral blood mononuclear cells (PBMC). IL-21 in the supernatant of Tfh were quantified after stimulation by Phorbol 12-myristate 13-acetate (PMA) / ionomycin. Then, the frequency of IL-21-producing cells and molecule expression of Tfh was analyzed after stimulating PBMC. Effect by IL-21 on B and Tfh cell was analyzed. These analyses were mainly performed by flow cytometry.[Results] The production of IL-21 by Tfh upon stimulation from MG patients was about nine times higher than that from HC (MG vs. HC, p=0.018). Additionally, the frequency of IL-21-producing cells was significantly higher within ICOShigh Tfh than within ICOSlow Tfh (16.1±7.2 % vs. 7.6±4.0%, p=0.037). Interestingly, IL-21 improved B cells survival and maintained CXCR5 expression on B and Tfh cells.[Conclusion] We discovered that IL-21 by Tfh maintains CXCR5 on B and Tfh cells. Likely, increased IL-21 production promotes Tfh and B cells homing to lymphoid organs and their interaction in MG.