The protective role of "super Th1 cells"-derived IL-22 in Th1-type airway inflammation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07544
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Hyogo Medical University
• Principal Investigator: Nakahira Masakiyo 兵庫医科大学, 医学部, 講師 (60454758)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: IL-18 / IL-22 / Th1細胞 / 気道炎症 / 高齢者喘息

Outline of Final Research Achievements

When stimulated with antigen+IL-18, Th1 cells produce IFN-γ and IL-13 (Th1 cells which acquired capability to produce IL-13 are referred to as “super Th1 cells”). Simultaneous production of IFN-γ and IL-13 by super Th1 cells induces Th1-type airway inflammation. The present study revealed that super Th1 cells produced IL-22, which contributed to the repair and maintenance of lung tissue in Th1-type airway inflammation. These results suggest that the severity of Th1-type airway inflammation appears to be regulated by the balance of the cytokines produced by super Th1 cells.
In addition, the present study also revealed that serum level of IL-18 was greater in aged mice compared to young mice and that Th1-type airway inflammation was emerged in aged mice carrying antigen-specific Th1 cells without intranasal IL-18 administration. These results indicate that IL-18 production increasing with age contributes to the development of Th1-type airway inflammation.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

高齢者喘息ではTh17応答が関与する好中球性炎症が多く見られるが、重症化しやすい好酸球+好中球性の混合顆粒球増加型も存在する。本研究で、マウスでは加齢に伴いsuper Th1細胞誘導因子IL-18の産生が増大すること、高齢マウスのIL-18は好酸球+好中球浸潤を特徴とするTh1型気道炎症を惹起可能であることが示された。この結果は、混合顆粒球増加型高齢者喘息の中にsuper Th1細胞によるものが含まれ、故にIL-18が高齢者喘息の治療標的となりうる可能性を示唆する。また、Th1型気道炎症でのIL-22の肺組織保護作用も明らかになったことから、IL-22が治療手段となりうる可能性も示唆された。