Crosstalk between gut immunity after hematopoietic stem cell transplantation stem cell transplantation and TLR

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16965
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Aichi Medical University
• Principal Investigator: UCHINO KAORI 愛知医科大学, 医学部, 講師 (70714872)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: TLR / 造血細胞移植 / UNC93B1

Outline of Final Research Achievements

UNC93B1 is a key regulator of TLRs. We investigated the influence of the UNC93B1 single-nucleotide polymorphism (SNP) rs308328 (T>C) on transplant outcomes in a cohort of 237 patients undergoing unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies. The donor UNC93B1 C/C genotype was associated with a better 3-year overall survival than the donor UNC93B1 C/T or T/T genotype. An analysis of the UNC93B1 rs308328 genotype may therefore be useful for selecting the donor, estimating the prognosis, and creating therapeutic strategies after allogeneic SCT. We also analyzed the variety of guts microbiome with stool of BMT patients. However, there were no significant differences between before and after BMT. One of the reasons why we couldn’t the get the significant difference is that the number of patients who agreed this research was fewer than expected. We continue to collect the samples and analysis of guts microbiome of the BMT patients.

Free Research Field

造血細胞移植

Academic Significance and Societal Importance of the Research Achievements

Unc 93 homolog B1 (Unc93B1)はTLR7とTLR9を核酸認識の場に運搬し、免疫応答バランスに影響する重要なタンパク質であるが、このUNC93B1が造血細胞移植後転帰に関わることを今回初めて証明した。TLR関連遺伝子がTLRの免疫応答バランスに影響している可能性があり、同種移植に適切な免疫応答バランスがそれぞれのTLRごとに存在していると考えられた。TLR関連遺伝子多型の機能や免疫構築における役割が解明できれば、ドナー選定、予後予測、合併症予防に役立つことが期待される。