Tasuku Kawano1, Ryusuke Ouchi1, Takahiro Ishigaki1, Chiaki Masuda1, Tomomitsu Miyasaka1, Yuichi Ohkawara2, Nobuo Ohta3, Motoaki Takayanagi1, Tomoko Takahashi1, Isao Ohno4. 1. Division of Pathophysiology, Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Japan. 2. Division of Experimental Allergy and Immunology, Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Tohoku Medical Pharmaceutical University, Sendai, Japan. 3. Division of Otorhinolaryngology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan. 4. Center for Medical Education, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
Abstract
BACKGROUND: Bronchial asthma is characterized by type 2 T helper (Th2) cell inflammation, essentially due to a breakdown of immune tolerance to harmless environmental allergens. Etiologically, experiences of psychological stress can be associated with a heightened prevalence of asthma. However, the mechanisms underlying stress-related asthma development are unclear. In this study, we examined whether psychological stress increases susceptibility to allergic asthma by downregulating immune tolerance. METHODS: Female BALB/c mice were sensitized with ovalbumin/alum, followed by ovalbumin inhalation. Ovalbumin inhalation induced immune tolerance before sensitization occurred. Some mice were exposed to restraint stress during tolerance induction or sensitization. Asthma development was evaluated by airway responsiveness, inflammation, cytokine expression, and IgE synthesis. Sensitization was evaluated by measuring proliferation and cytokine production by splenocytes. The effects of stress exposure on the numbers and functions of dendritic cells and regulatory T (Treg) cells in bronchial lymph nodes and spleens were evaluated. To investigate the role of endogenous glucocorticoid in inhibiting immune tolerance after stress exposure, we examined the effects of (i) a glucocorticoid-receptor antagonist administered prior to stress exposure, and (ii) exogenous gluco-corticoid (instead of stress exposure). RESULTS: 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 tolerogenic dendritic and Treg cell numbers. The effects of stress exposure on tolerized mice were abolished by administering a glucocorticoid-receptor antagonist and reproduced by administering exogenous glucocorticoid without stress. CONCLUSIONS: Our findings suggested that psychological stress can potentially increase allergic asthma susceptibility by inhibiting immune tolerance.
BACKGROUND: Bronchial asthma is characterized by type 2 T helper (Th2) cell inflammation, essentially due to a breakdown of immune tolerance to harmless environmental allergens. Etiologically, experiences of psychological stress can be associated with a heightened prevalence of asthma. However, the mechanisms underlying stress-related asthma development are unclear. In this study, we examined whether psychological stress increases susceptibility to allergic asthma by downregulating immune tolerance. METHODS: Female BALB/c mice were sensitized with ovalbumin/alum, followed by ovalbumin inhalation. Ovalbumin inhalation induced immune tolerance before sensitization occurred. Some mice were exposed to restraint stress during tolerance induction or sensitization. Asthma development was evaluated by airway responsiveness, inflammation, cytokine expression, and IgE synthesis. Sensitization was evaluated by measuring proliferation and cytokine production by splenocytes. The effects of stress exposure on the numbers and functions of dendritic cells and regulatory T (Treg) cells in bronchial lymph nodes and spleens were evaluated. To investigate the role of endogenous glucocorticoid in inhibiting immune tolerance after stress exposure, we examined the effects of (i) a glucocorticoid-receptor antagonist administered prior to stress exposure, and (ii) exogenous gluco-corticoid (instead of stress exposure). RESULTS: 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 tolerogenic dendritic and Treg cell numbers. The effects of stress exposure on tolerized mice were abolished by administering a glucocorticoid-receptor antagonist and reproduced by administering exogenous glucocorticoid without stress. CONCLUSIONS: Our findings suggested that psychological stress can potentially increase allergic asthma susceptibility by inhibiting immune tolerance.
Authors: Gerasimos N Konstantinou; Christopher Koulias; Konstantinos Petalas; Michael Makris; George N Konstantinou Journal: J Asthma Allergy Date: 2022-09-10