Development of allergic asthma with the impairment of immune tolerance caused by psychological stress

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16212
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Tohoku Medical and Pharmaceutical University
• Principal Investigator: KAWANO TASUKU 東北医科薬科大学, 薬学部, 講師 (20584452)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: アレルギー / 喘息 / 精神的ストレス / 免疫寛容 / 幼少期 / 成人期 / Treg / Th2

Outline of Final Research Achievements

The aim of this project is the elucidate whether psychological stress increases susceptibility to allergic asthma by downregulating immune tolerance. Asthma was examined using OVA-sensitized model mice. The effects of stress exposure on the numbers and functions of regulatory T (Treg) cells in bronchial lymph nodes were evaluated. To investigate the role of endogenous glucocorticoid in inhibiting immune tolerance after stress exposure. Asthmatic responses and Th2-biased sensitization, which were suppressed in tolerized mice, re-emerged in tolerized mice stressed during tolerance induction in association with decreased Treg cell numbers. The effects of stress exposure on tolerized mice were abolished by administering a glucocorticoid-receptor antagonist. These findings suggested that psychological stress can potentially increase allergic asthma susceptibility by inhibiting immune tolerance.

Free Research Field

アレルギー

Academic Significance and Societal Importance of the Research Achievements

アレルギー性疾患は、遺伝的要因と環境要因の相互作用を背景として、複雑かつ多様な病態を示す事から「症候群」の概念が提唱され、発症年齢や重症度、炎症タイプ、治療反応性などから、様々なフェノタイプが報告されている。従って、精神的ストレスから喘息発症への機序を明らかにする本研究は、ストレス誘発性の新たなフェノタイプ『psychiatry phenotype』として確立するための基盤となる。また、本研究によるストレス性免疫寛容破綻機構の解明は、免疫寛容の回復・誘導を目的として現在汎用されている免疫療法を補強するシステムの創生、および免疫寛容破綻を予防する方法の確立に貢献することが期待できる。