Amino acid transporter Slc7a5 regulates inflammatory responses of human B cells

Research Project

Project/Area Number	17K16211
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Collagenous pathology/Allergology
Research Institution	Oita University
Principal Investigator	Torigoe Masataka 大分大学, 医学部, 医員 (40793146)
Project Period (FY)	2017-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000) Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000) Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords	膠原病 / B細胞 / Slc7a5 / アミノ酸トランスポーター / mTORC1 / アミノ酸トランスポーターSlc7a5 / ｍTORC1 / ヒトBリンパ球 / 自己免疫疾患 / ヒトB細胞 / L-Leucine / 免疫学 / シグナル伝達
Outline of Final Research Achievements	B cells contribute to the pathogenesis of various rheumatic diseases, through the production of autoantibodies and inflammatory cytokines. Corticosteroids and various immunosuppressive drugs are the main stay for the treatment of rheumatic diseases. However, refractory cases are sometimes experienced, who exhibit adverse events or resistance to conventional therapy. Thus, development of a novel therapy is desirable. Recently, it was reported that an amino acid transporter, Slc7a5 regulates the activity of cancer cells and certain immune cells through regulating amino acid transport. Meanwhile, the expression and role of Slc7a5 in B cells have never been investigated. In the present study, we revealed that Slc7a5 was closely involved in the immune response of human B cells, and could be a new strategy to control B cell function.
Academic Significance and Societal Importance of the Research Achievements	膠原病治療の分野では、多くの疾患において現在もステロイドや免疫抑制薬がその中心である。しかし、ステロイドは高用量や長期の使用により骨粗鬆症や皮膚菲薄化などが問題となり、免疫抑制薬も様々な副作用の為に中止されることも少なくない。また、これらの治療薬でも病態制御の困難な症例も時に経験される。B細胞は、多くの膠原病の病態形成において主要な役割を有している。アミノ酸トランスポーターSlc7a5によるB細胞制御は既存の治療法に無い全く新しい戦略であり、難治例での現状打開も期待されうる。