Physiological significance of trained-innate lymphoid cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19368
• 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: Akita University
• Principal Investigator: Ebihara Takashi 秋田大学, 医学系研究科, 教授 (20374407)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: Trained immunity / ILC1 / ILC2 / ILC3 / NK細胞

Outline of Final Research Achievements

Group 2 innate lymphoid cells (ILC2s) play a pivotal role in initiating allergic inflammation through the secretion of Th2 helper cytokines. Following activation by allergic stimuli, a subset of ILC2s remains within the mucosal tissue. Upon re-exposure to allergens, these "trained" ILC2s mount a robust response. In our study, we investigated the fate of activated ILC2s, whether they transition to trained ILC2s or undergo cell death. To track the activated ILC2s, we utilized fate tracer mice expressing tdTomato in KLRG1-, PD-1-, or TIGIT-expressing activated ILC2s. Our findings indicate that TIGIT+ ILC2s, representing highly activated cells, are swiftly eliminated from the airways through interaction with CD155+ alveolar macrophages. We propose to term this type of cell death "activation-induced cell death of ILC2s" (ILC2 AICD). This newly discovered mechanism offers a promising approach to mitigating chronic airway allergy.

Free Research Field

Immunology

Academic Significance and Societal Importance of the Research Achievements

ILC2は活性化を維持したまま非常によく増殖することが知られており、アレルギー炎症の増悪に寄与する細胞と知られていた。しかし、今まで活性化したILC2がどのように除去されていくのか明らかになっていなかった。私達の研究結果により活性化ILC2はTIGITを発現した後にマクロファージにより生体内から除去されていくことが明らかになった。活性化ILC2にAICDを誘導する手段を開発できれば、慢性アレルギー炎症に対する新しい治療戦略となるかもしれない。