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Deciphering the immune mechanism of increased airway allergic disease in menopause

Grant number: 21/06751-4
Support Opportunities:Research Grants - Young Investigators Grants - Phase 2
Duration: May 01, 2022 - April 30, 2027
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Caroline Marcantonio Ferreira
Grantee:Caroline Marcantonio Ferreira
Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
Associated researchers:Anderson de Sá Nunes ; Gilles Landman ; Niels Olsen Saraiva Câmara ; Patricia Xander Batista ; Vinicius de Andrade Oliveira
Associated research grant:12/50410-8 - Effects of short-chain fatty acids produced by probiotic bacteria in the prophylaxis and treatment of allergic airway inflammation, AP.JP
Associated grant(s):22/08144-0 - Multi-user equipment approved in grant 21/06751-4: BD FACSymphony A1 Cell Analyzer, AP.EMU
Associated scholarship(s):23/06629-0 - Deciphering the immune mechanism of increased airway allergic disease in menopausal, BE.PQ
23/06670-0 - Deciphering the immune mechanism of increased airway allergic disease in menopausal, BP.PD
23/03609-8 - Deciphering the Immune Mechanism of Increased Airway Allergic Disease in Menopausal Phase, BP.IC
+ associated scholarships 23/03614-1 - Deciphering the Immune Mechanism of Increased Airway Allergic Disease in Menopausal Phase, BP.IC
22/12955-4 - Deciphering the immune mechanism of increased airway allergic disease in menopausal, BP.DD
22/09076-9 - Deciphering the Immune Mechanism of Increased Airway Allergic Disease in Menopausa, BP.TT
22/05797-3 - Deciphering the immune mechanism of increased airway allergic disease in menopausal, BP.DD - associated scholarships

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 mechanisms by which these probiotics or SCFAs can prevent exacerbation of allergic airway inflammation 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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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
NASCIMENTO, CAROLINA MARTINS; CASARO, MATEUS CAMPOS; PEREZ, EVELYN ROXANA; RIBEIRO, WILLIAN RODRIGUES; MAYER, MARCIA PINTO ALVES; ISHIKAWA, KARIN HITOMI; LINO-DOS-SANTOS-FRANCO, ADRIANA; PEREIRA, JOICE NAIARA BERTAGLIA; FERREIRA, CAROLINE MARCANTONIO. Experimental allergic airway inflammation impacts gut homeostasis in mice. HELIYON, v. 9, n. 6, p. 11-pg., . (19/12324-1, 21/06751-4)

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