Role of MAIT cells in autoreactive B cell response to DNA.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08807
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Juntendo University
• Principal Investigator: Chiba Asako 順天堂大学, 医学部, 准教授 (40532726)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 全身性エリテマトーデス / MAIT細胞 / 自己抗体 / IFNα / 単球

Outline of Final Research Achievements

The production of anti-dsDNA antibodies is a hallmark of systemic lupus erythematosus (SLE). However, it is not well understood which cells activate dsDNA reactive B cells. This study demonstrated that MAIT cells directly activate B cells to produce anti-dsDNA antibodies. Inhibition of MAIT cell activation in vivo resulted in a reduction of anti-dsDNA antibodies even after the onset of SLE. IFNα is known to be the most important cytokine in the pathogenesis of SLE. We have previously shown that MAIT cells are activated by IFNα and that lupus monocytes are capable of producing IFNα upon activation of the STING pathway. This study also showed that increased IFNα production by lupus monocytes was associated with accelerated cellular senescence of these cells. These findings suggest that increased IFNα production by monocytes and activated MAIT cells may contribute to the pathogenesis of SLE.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

MAIT細胞は、非ペプチド自己抗原であるdsDNAに対するB細胞応答を促進することを明らかにした。マウスモデルを用い、生体内でMAIT細胞の活性化を抑えることにより、抗dsDNA抗体の産生が低下することを示した。更に、SLEの病態形成やMAIT細胞の活性化に重要なIFNαの産生源として、細胞老化が亢進した単球の可能性を示した。MAIT細胞や細胞老化状態にある単球は、SLEの重症化や再発を抑える新規治療法の標的として発展する可能性が明らかとなり、社会的意義が大きい。