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Roles of cleaved immunoglobulins in pathophysiology of lepromatous leprosy

Research Project

Project/Area Number 19K08946
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54030:Infectious disease medicine-related
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

Ato Manabu  国立感染症研究所, ハンセン病研究センター 感染制御部, 部長 (20392318)

Project Period (FY) 2019-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords免疫グロブリン / ハンセン病 / 免疫グロブリン様受容体
Outline of Research at the Start

ハンセン病は、世界で年間20万人以上の新規患者が認められ、依然として国際的に重要な公衆衛生学的課題である。
本研究は、L型ハンセン病病変部位のLILRA2発現および免疫グロブリン部分分解産物の存在について、その存在が認められた場合は、ヒトから分離したLILRA2発現白血球亜群細胞等を用いて、免疫グロブリン分解産物がらい菌感染免疫応答へ及ぼす影響を解析し、L型ハンセン病の病態形成に関与するを解明することを目的とする。これらが判明すれば、ハンセン病の病態の解明につながり、ハンセン病の早期診断と早期治療の開始、発症ハイリスク者の発症予防対策等に対し、大いに貢献することが可能となる。

Outline of Final Research Achievements

Host immunity plays a role in the symptoms of leprosy and the severity of infection. However, it is unclear what molecular mechanisms are responsible for the predominance of Th2 immune responses in Lepromatoid leprosy. Recently, the immunoglobulin-like receptor LILRA2 was identified as a candidate biomarker for Lepromatoid-type leprosy. To analyze LILRA2 expression in leprosy lesions, we attempted to detect its binding by LILRA2-Fc fusion protein in 13 leprosy skin tissue samples. As a result, positive cells were found in leprosy skin tissues, but positive reactions were observed in mast cells, not in infected cells. Because mast cells nonspecifically react with some ligands , further investigation is needed to determine the relationship between this finding and the pathogenesis of leprosy.

Academic Significance and Societal Importance of the Research Achievements

本研究は、L型ハンセン病病変部位のLILRA2発現および免疫グロブリン部分分解産物の存在について確認し、ヒトから分離したLILRA2発現白血球亜群細胞及びハンセン病動物感染モデルを用いて、免疫グロブリン分解産物がらい菌感染免疫応答へ及ぼす影響を解析し、L型ハンセン病の誘導因子を解明することを目的とする。これらが判明すれば、ハンセン病の病態の解明につながり、ハンセン病の予防、早期診断と早期治療の開始、発症ハイリスク者の発症予防対策等に対し、大いに貢献することが可能となる。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (3 results)

All 2024 2023 2020

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (1 results)

  • [Journal Article] Case Report: Borderline Lepromatous Leprosy Therapy Complicated by Type 1 Leprosy Reaction and Adverse Reactions with Dapsone and Clofazimine2024

    • Author(s)
      Matono Takashi、Suzuki Shotaro、Mori Shuichi、Ato Manabu
    • Journal Title

      The American Journal of Tropical Medicine and Hygiene

      Volume: 110 Issue: 3 Pages: 483-486

    • DOI

      10.4269/ajtmh.22-0637

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PGL-III, a Rare Intermediate of <i>Mycobacterium leprae</i> Phenolic Glycolipid Biosynthesis, Is a Potent Mincle Ligand2023

    • Author(s)
      Ishizuka Shigenari、van Dijk J. Hessel M.、Kawakita Tomomi、Miyamoto Yuji、Maeda Yumi、Goto Masamichi、Le Calvez Guillaume、Groot L. Melanie、Witte Martin D.、Minnaard Adriaan J.、van der Marel Gijsbert A.、Ato Manabu、Nagae Masamichi、Cod?e Jeroen D. C.、Yamasaki Sho
    • Journal Title

      ACS Central Science

      Volume: 9 Issue: 7 Pages: 1388-1399

    • DOI

      10.1021/acscentsci.3c00040

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Elongation and septal formation of M. leprae.2020

    • Author(s)
      Fukutomi Y, Yamamoto K, and Ato M.
    • Organizer
      第93回日本細菌学会総会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2025-01-30  

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