Elucidation of the mechanisms in the strain specific Th2 response in BALB/c mice

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K21522
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Kanazawa University
• Principal Investigator: Watarai Hiroshi 金沢大学, 医学系, 教授 (70415339)
• Project Period (FY): 2020-07-30 – 2024-03-31
• Keywords: iNKT細胞 / Th2 / アレルギー

Outline of Final Research Achievements

It is well known that BALB/c mice have a dominant Th2 response compared to C57BL/6 mice, but the details of this phenomenon are largely unknown. Since iNKT2 subsets are significantly abundant in iNKT cells in BALB/c mice, we established IL-17RB-deficient mice from both backgrounds and analyzed the differences in their developmental pathways. IL-17RB-deficient mice with a B6 background showed a marked decrease in iNKT2 cells in both periphery and thymus, suggesting that IL-25/IL-17RB axis is essential for development and maintenance. Interestingly however there was no significant difference in the number of iNKT2 cells in the periphery of BALB/c background. In the thymus of BALB/c background, a significant increase of iNKT cells was observed in IL-17RB-deficient mice. The increased population was distinct from iNKT1/2/17 subsets and phenotypically RORγt+ PLZFint T-bet- CD24+ CD44int CD69-, a precursor iNKT2-like cells are appeared.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

BALB/cマウスにはB6マウスに存在しないiNKT2サブセットが存在し、iNKT2サブセットはIL-17RB非依存的に分化発生し得ることを明らかとした。iNKT2細胞は（特に小児期に）様々なアレルギー炎症に関与していることが知られるため、その機能や分化発生経路の一端を明らかにできたことは学術的に意義深い。また遺伝的背景の相違によって異なるiNKT2細胞が分化発生するという結果は、標的となる細胞に個人差があるという裏付けとなるため、様々なアレルギー治療やその制御戦略上重要であり、その社会的要請や意義も高いと考えられる。