Regulation of pathogenic autoantibody production by Nogo

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K08874
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Aichi Medical University
• Principal Investigator: Inui Masanori 愛知医科大学, 医学部, 講師 (80443985)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Keywords: 自己抗体 / 自己免疫疾患

Outline of Final Research Achievements

I have shown that Nogo, an endoplasmic reticulum membrane protein, is expressed on macrophages and is essential for the induction of intracellular signaling throught nucleic acid-sensing TLRs. I generated Nogo-deficient mice backcrossed to BXSB mice, a disease model with SLE-like autoimmune symptoms, and found that BXSB.Nogo-deficient mice showed significantly decreased anti-ds-DNA IgG antibody titer while total IgG antibody titer in blood was comparable to BXSB mice. On the other hand, both total IgM and anti-ds-DNA IgM antibody titer in blood were significantly decreased in BXSB.Nogo-deficient mice. These results suggest that Nogo could regulate the class switch recombination to IgG in autoantibody-producing B cells.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

抗体産生細胞であるB細胞の寛容機構の維持が破綻すると，病原性自己抗体の産生が誘導され全身性エリテマトーデス（SLE）など様々な自己免疫疾患の発症につながる。そのためB細胞の寛容誘導機構を解明することは自己免疫疾患の新規な治療法の開発に不可欠である。申請者は小胞体膜タンパクであるNogoが自己抗体産生，さらにはクラススイッチに関与することを明らかにした。本研究課題の遂行により，免疫寛容の成立・維持を制御する新規な概念を提唱できた。