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Gut-lung axis: understanding the immune dialogue between barrier tissues in the development of disease

Grant number: 21/06881-5
Support Opportunities:Research Grants - Young Investigators Grants - Phase 2
Duration: February 01, 2022 - January 31, 2027
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Denise Morais da Fonseca
Grantee:Denise Morais da Fonseca
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers:Ana Marcia de Sá Guimarães ; Ana Maria Caetano de Faria ; Ana Paula Lepique ; Ana Paula Rocha Veiga ; Anderson de Sá Nunes ; Andrea Pires dos Santos ; Aristóteles Góes Neto ; Flávio Vieira Loures ; Jofer Andree Zamame Ramirez ; Maria Regina D'Império Lima ; Timothy Wesley Hand
Associated research grant:15/25364-0 - Impact of infection-induced immunological scarring on the long-term host metabolic homeostasis, AP.JP
Associated scholarship(s):23/15980-2 - Impact of infection-induced immunological scar for the development of colon-rectal cancer, BP.IC
23/04035-5 - Contribution of adipose tissue compartments to oral vaccine response, BP.MS
23/00189-8 - Effect of selenium-enriched probiotic on mucosal tissues, BP.MS
+ associated scholarships 23/00532-4 - Immunological scar development and impairment of the tissue-specific immune response after COVID-19, BP.PD
23/00534-7 - Gut-lung Axis: understanding the effects of immunological scar for lung tumor development, BP.PD
22/10275-6 - Gut-lung axis: understanding the effects of immunological scar for lung tumor development, BP.DD - associated scholarships


Mucosal tissues are endowed with a specialized immune system with specific effector mechanisms designed to respond to the enormous range of regional challenges while maintaining tissue homeostasis. In this sense, specialized cells and immune mediators are found in each mucosal tissue. Classically, subtypes of dendritic cells, T lymphocytes, and antibody-producing B cells are differently regulated in the mucosa. Our research group has been working to identify non-classical mechanisms that act not only in maintaining tissue homeostasis but also in the communication between barrier tissues, such as the intestine and the lung. The importance of the gut-lung axis in disease control and promotion has been studied in different contexts, focusing on mechanisms involving cell trafficking, changes in the microbiota composition and microbial metabolites. In this context, at the Mucosal Immunology Laboratory, we study how episodes of infection affecting the structure of the mesentery and lymphatics impact in host immunity and metabolism, and in the integration of the immune response between the different barrier tissues. We believe that the mechanisms mediating the immunological communication between the intestinal and pulmonary mucosa have a confluence point in the mesentery. This proposal aims at understanding the mechanisms involved in the immune dialogue between mucosal tissues, particularly the gut and lung. For this, we will study the functional impact of infectious and non-infectious environmental challenges in the gut for lung immunity, focusing on the involvement of the microbiota and its metabolites, adjacent adipose tissue compartments, lymphatic vessels, and micro RNAs. This proposal will be divided into two major aims. In the first one, we will address the long-term effects of acute intestinal infection for lung immunity. In the second aim, we will study the consequences of dietary changes for lung immune homeostasis, emphasizing immunity against lung (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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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)
DE SOUZA, WILLIAM DANILO FERNANDES; ZORZELLA-PEZAVENTO, SOFIA FERNANDA GONCALVES; AYUPE, MARINA CACADOR; SALGADO, CAIO LOUREIRO; OLIVEIRA, BERNARDO DE CASTRO; MOREIRA, FRANCIELLY; DA SILVA, GUILHERME WILLIAM; MURARO, STEFANIE PRIMON; DE SOUZA, GABRIELA FABIANO; PROENCA-MODENA, JOSE LUIZ; et al. Lung Inflammation Induced by Inactivated SARS-CoV-2 in C57BL/6 Female Mice Is Controlled by Intranasal Instillation of Vitamin D. CELLS, v. 12, n. 7, p. 24-pg., . (19/13916-0, 20/04558-0, 19/07771-9, 21/12768-7, 19/12691-4, 21/06881-5)
DE SOUZA, WILLIAM DANILO FERNANDES; DA FONSECA, DENISE MORAIS; SARTORI, ALEXANDRINA. COVID-19 and Multiple Sclerosis: A Complex Relationship Possibly Aggravated by Low Vitamin D Levels. CELLS, v. 12, n. 5, p. 28-pg., . (21/06881-5)
SAYEDAHMED, EKRAMY E.; ARAUJO, MARCELO VALDEMIR; SILVA-PEREIRA, TAIANA TAINA; CHOTHE, SHUBHADA K.; ELKASHIF, AHMED; ALHASHIMI, MARWA; WANG, WEN-CHIEN; SANTOS, ANDREA P.; NAIR, MEERA SURENDRAN; GONTU, ABHINAY; et al. Impact of an autophagy-inducing peptide on immunogenicity and protection efficacy of an adenovirus-vectored SARS-CoV-2 vaccine. MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT, v. 30, p. 14-pg., . (19/13916-0, 19/12691-4, 20/09149-0, 20/07251-2, 21/06881-5, 21/02736-0)

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