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Multi-user equipment approved in grant 21/06751-4: BD FACSymphony A1 Cell Analyzer

Abstract

Asthma has been extensively studied in women of reproductive age, while the menopausal age range has been less studied. Among women over 50 years old of age, menopause can either coin-cide with the onset of asthma, or in women with pre-existing asthma, be associated with the worsening of symptoms. Recently, our lab published findings showing that the re-exposure of ovariectomized (OVx) allergic mice to antigen exacerbates lung inflammation and decreases air-way function, however the mechanisms involved are not clear. In addition, preventive but not therapeutic supplementation with acetate-producing bacterium is able to prevent the increased recall response and airway inflammation in OVx allergic mice. Short chain fatty acid (SCFA), such as acetate, has been implicated in the impaired ability of dendritic cells (DCs) to promote Th2 cell effector function and increase levels of T-regulatory (Tregs) cells. However, the mecha-nisms by which these probiotics or SCFAs can prevent exacerbation of allergic airway inflamma-tion in OVx mice needs to be identified. Recently, allergen-specific resident memory T cells (TRM) have been found to accumulate after HDM exposure and mediate experimental asthma symptoms upon re-challenge. We show in this proposal preliminary data that transcription factor, IRF4+, in CD11c+ conventional type 2 DC cells (cDC2) is necessary for the development of Th2 differentiation. Interestingly, estrogen receptor signaling promotes dendritic cell differentiation by upregulating IRF4. Our central hypothesis is that menopause induces exacerbation of pre-existing asthma through induction of IRF4+ cDC2s and Th2-skewed TRM cells, and that SCFA mute this response. Understanding the mechanisms by which the decline of female sex hormones promotes the worsening of asthma is key to the development of new targets for therapeutics. (AU)

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