Exploration for immunoregulatory microRNAs based on genetic polymorphism associated with hematopoietic stem cell transplantation

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K08343
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Aichi Medical University
• Principal Investigator: Takami Akiyoshi 愛知医科大学, 医学部, 教授 (80324078)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 機能的遺伝子多型

Outline of Final Research Achievements

In this study, the functional roles of immunomodulatory gene polymorphisms in the 5’-untranslated region (NLRP3, ADMTS13, UNC93B1, HO-1), which the principal investigator has previously shown affect survival outcomes after allogeneic hematopoietic stem cell transplantation, were demonstrated. In particular, it was found that the G and C alleles in the NLRP3 rs10754558 (G > C) have high inducibility of NLRP3 / IL-1b and low inducibility of NLRP3 / IL-1b, respectively. In addition, allogeneic hematopoietic stem cell transplant recipients with the NLRP3 rs10754558 G allele were suggested to have increased mortality from transplant-related complications due to their high IL-1b inducibility. These results will also lead to the development of new targeted therapies for solid cancers, autoimmune diseases, and severe infectious diseases in which immunomodulatory gene polymorphisms are involved in their onset and progression of diseases.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

同種造血幹細胞移植は白血病など血液難病の根治を期待して行われる。しかし、重症感染症や拒絶反応、再発のため、長期生存率は50%にとどまる。本研究において、下流非翻訳領域の機能性免疫調整遺伝子多型を制御することにより、同種造血幹細胞の成功率が飛躍的に高まる可能性が示された。さらに今回の研究成果は、同種造血幹細胞移植にとどまらず、疾患の発症や進展に免疫調整遺伝子多型が関与する固形がんや自己免疫疾患、重症感染症に対する新規標的治療法開発への波及効果も期待される。