Elucidation of qualitative abnormalities of autoreactive B cells in patients with SLE

Research Project

Project/Area Number	17K16219
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Collagenous pathology/Allergology
Research Institution	University of Occupational and Environmental Health, Japan
Principal Investigator	Yoshikawa Maiko 産業医科大学, 医学部, 非常勤助教 (70596676)
Project Period (FY)	2017-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	全身性エリテマトーデス / B細胞 / ケモカイン受容体 / CXCR3 / CXCR5 / SLE
Outline of Final Research Achievements	In this study, we focused on the expression of chemokine receptors in B cells to assess the qualitative abnormalities of autoreactive B cells in patients with SLE. The peripheral blood of patients with SLE showed higher levels of CXCR5-CXCR3- B cells and CXCR5-CXCR3+ B cells. CXCR5-CXCR3+ B cell levels were elevated in patients with active SLE, which decreased with improving disease conditions. Furthermore, in vitro experiments revealed that type I/II interferons (IFNs) are a potent inducer of effector memory B cells involving abnormal chemokine receptor expression, suggesting their involvement in B cell infiltration into tissues. These results demonstrate the importance of IFNs in qualitative abnormalities in SLE B cells.
Academic Significance and Societal Importance of the Research Achievements	本研究の研究成果はSLE病態におけるI型およびII型IFN の重要性の再認識の観点から学術的意義があると考える。現在、SLE患者に対する抗IFNAR抗体の有効性が臨床試験で示されており、抗IFN-γ抗体の試験も進行中であるが、活動性ループス腎炎患者の腎生検組織でCXCR3+B細胞浸潤を認めたことから、T-betなどの転写因子やCXCR3などのケモカイン受容体による病態制御、治療応用へ展開する可能性もあり、社会的意義は大きいと考える。