Analysis of the effect of cytokine production by autoantigen-reactive B cells in systemic sclerosis on other immune systems.

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22925
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0903:Organ-based internal medicine and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Fukasawa Takemichi 東京大学, 医学部附属病院, 助教 (80884056)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 自己反応性B細胞 / サイトカイン / 全身性強皮症 / T細胞 / microfluidics / 単一細胞解析

Outline of Final Research Achievements

In this study, we used original microspace-based techniques and methodologies to elucidate the function and role of autoreactive B cells in systemic sclerosis (SSc). Regarding the relationship between affinity to topoI antigen and cytokine production capacity, the proportion of B cells producing inflammatory cytokines such as IL-6 and IL-23 was higher in high affinity B cells, and the amount produced was also higher. Similarly, low affinity B cells produced a higher percentage of B cells that produced IL-10 and IL-35 inhibitory cytokines, and the amount produced was also higher. The former was also shown to induce Th17 cells and the latter Treg cells.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

本研究は、自己抗原反応性B細胞の機能を明らかとすることで、数あるB細胞集団中から、病原性を有するB細胞集団を明らかとする。さらに我々の技術では、少数の自己抗原反応性B細胞のタンパク分析を可能としており、表面抗原の分析によって新たな治療ターゲットの同定につながることが期待される。このような研究は他に類が無く、他の自己免疫疾患においても応用可能であることから、革新的かつ創造的な研究となることが期待される。