Identification of testicular autoantigen in autoimmune orchitis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18572
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Tokyo Medical University
• Principal Investigator: Nagahori Kenta 東京医科大学, 医学部, 助教 (50759561)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 精巣 / 自己免疫精巣炎 / 精子形成障害

Outline of Final Research Achievements

Clinically, 60% of male infertility cases are categorized as idiopathic spermatogenic disturbance. In previous studies, lymphocytic infiltration and immune deposits were present in several testis biopsy specimens, indicating that inflammatory or immunological factors contribute to the occurrence of the lesions. However, autoimmunogenic antigens that induce autoimmune orchitis have not yet been identified. In this study, we found that immunization of male mice with testis-specific autoimmunogenic antigen (Hspa4l and Git1) was sufficient to induce experimental autoimmune orchitis. In addition, we demonstrated that both antibodies and T-cell activity against Hspa4l and Git1 are closely related to the pathogenesis of EAO, suggesting their utility as biomarkers of male infertility in humans.

Free Research Field

生殖免疫学

Academic Significance and Societal Importance of the Research Achievements

特発性精子形成障害の精巣生検において、免疫グロブリンや補体沈着が認められる症例、つまり自己免疫性精子形成障害は多く報告されているが、その原因となる自己抗原の詳細については未だに不明である。本研究では実験的自己免疫精巣炎を誘導する因子を発見した。本研究の成果は、自己免疫性精巣炎の病因を理解するための新しいアプローチ法を提供し、自己免疫に基づく精子形成の障害に対する新しい診断法および検査法・治療法など新たな技術開発に対する重要な基礎的知見を提供する。