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Deciphering the Immune Mechanism of Increased Airway Allergic Disease in Menopausal Phase

Grant number: 23/03614-1
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): June 01, 2023
Effective date (End): May 31, 2024
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Caroline Marcantonio Ferreira
Grantee:Isabela Aguiar Silva
Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
Associated research grant:21/06751-4 - Deciphering the immune mechanism of increased airway allergic disease in menopause, AP.JP2


Asthma has been extensively studied in women of reproductive age, while the menopausal agerange has been less studied. Among women over 50 years old of age, menopause can eithercoincide with the onset of asthma, or in women with pre-existing asthma, be associated withthe worsening of symptoms. Recently, our lab published findings showing that the re-exposureof ovariectomized (OVx) allergic mice to antigen exacerbates lung inflammation and decreasesairway function, however the mechanisms involved are not clear. In addition, preventive butnot therapeutic supplementation with acetate-producing bacterium is able to prevent theincreased 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) topromote Th2 cell effector function and increase levels of T-regulatory (Tregs) cells. However,the mechanisms by which these probiotics or SCFAs can prevent exacerbation of allergicairway inflammation in OVx mice needs to be identified. Recently, allergen-specific residentmemory T cells (TRM) have been found to accumulate after HDM exposure and mediateexperimental asthma symptoms upon re-challenge. We show in this proposal preliminary datathat transcription factor, IRF4+, in CD11c+ conventional type 2 DC cells (cDC2) is necessaryfor the development of Th2 differentiation. Interestingly, estrogen receptor signaling promotesdendritic cell differentiation by upregulating IRF4. Our central hypothesis is that menopauseinduces exacerbation of pre-existing asthma through induction of IRF4+ cDC2s and Th2-skewed TRM cells, and that SCFA mute this response. Understanding the mechanisms bywhich the decline of female sex hormones promotes the worsening of asthma is key to thedevelopment of new targets for therapeutics.

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