Effect of short chain fatty acids on the function of type 3 innate lymphoid cells: involvement of the FFAR2 receptor in this process

• Grant number: 18/02208-1
• Support type: Scholarships in Brazil - Master
• Effective date (Start): April 01, 2018
• Effective date (End): May 31, 2020
• Field of knowledge: Biological Sciences - Immunology
• Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Marco Aurélio Ramirez Vinolo
• Grantee: Laís Passariello Pral
• Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

ILC3 are innate lymphoid cells found primarily along the intestinal mucosa. These cells play a fundamental role in the direct and indirect interaction between the local microbiota and the host cells. Our hypothesis is that these cells are modulated by the action of products of the bacterial metabolism from the intestinal microbiota, the so-called short chain fatty acids (AGCCs). In this context, we aim to analyze whether the AGCCs and their FFAR2 receptor modulate the activation and production of cytokines by these cells. To do so, we will use models in vitro and in vivo. We will characterize the profile of ILCs present in the lamina propria of the small intestine, colon and lymph nodes of wild animals (WT) or deficient (KO) in protein FFAR2 and treated or not with antibiotics (method to reduce the intestinal concentration of AGCCs ). We will then isolate ILC3 (NCR + and NCR-) from reporter mice (RORyt Cre x mTmG) by sorting and we will analyze the production of IL-17 and IL-22 by these cells both in the presence or absence of AGCCs. These experiments will be done with cells isolated from FFAR2WT and KO animals. Finally, we will evaluate the in vivo effect of oral supplementation of sodium acetate (FFAR2 agonist) on mice with specific deletion of FFAR2 in cells expressing the Roryt transcription factor, which includes the ILC3. In these experiments we will evaluate clinical aspects, bacterial load in tissues, inflammatory alterations of the intestinal epithelium and the activated immune response profile. With the present project, we intend to advance the understanding of the mechanisms of interaction between microbiota and the cells of the host immune system. (AU)

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)

FACHI, JOSE LUIS; SECCA, CRISTIANE; RODRIGUES, PATRICIA BRITO; PINHEIRO DE MATO, FELIPE CEZAR; DI LUCCIA, BLANDA; FELIPE, JAQUELINE DE SOUZA; PRAL, LAIS PASSARIELLO; RUNGUE, MARCELLA; ROCHA, VICTOR DE MELO; SATO, FABIO TAKEO; SAMPAIO, ULLIANA; PEDROSA SILVA CLERICI, MARIA TERESA; RODRIGUES, HOSANA GOMES; SARAIVA CAMARA, NIELS OLSEN; CONSONNI, SILVIO ROBERTO; VIEIRA, ANGELICA THOMAZ; OLIVEIRA, SERGIO COSTA; MACKAY, CHARLES REAY; LAYDEN, BRIAN T.; BORTOLUCI, KARINA RAMALHO; COLONNA, MARCO; RAMIREZ VINOLO, MARCO AURELIO. Acetate coordinates neutrophil and ILC3 responses against C. difficile through FFAR2. JOURNAL OF EXPERIMENTAL MEDICINE, v. 217, n. 3 MAR 2020. Web of Science Citations: 0.

FACHI, JOSE LUIS; FELIPE, JAQUELINE DE SOUZA; PRAL, LAIS PASSARIELLO; DA SILVA, BRUNA KARADI; CORREA, RENAN OLIVEIRA; PEREIRA DE ANDRADE, MIRELLA CRISTINY; DA FONSECA, DENISE MORAIS; BASSO, PAULO JOSE; SARAIVA CAMARA, NIELS OLSEN; DE SALES E SOUZA, ERICKA LORENNA; MARTINS, FLAVIANO DOS SANTOS; SATO GUIMA, SUZANA EIKO; THOMAS, ANDREW MALTEZ; SETUBAL, JOAO CARLOS; MAGALHAES, YULI THAMIRES; FORTI, FABIO LUIS; CANDREVA, THAMIRIS; RODRIGUES, HOSANA GOMES; DE JESUS, MARCELO BISPO; CONSONNI, SILVIO ROBERTO; FARIAS, ALESSANDRO DOS SANTOS; VARGA-WEISZ, PATRICK; RAMIREZ VINOLO, MARCO AURELIO. Butyrate Protects Mice from Clostridium difficile-Induced Colitis through an HIF-1-Dependent Mechanism. CELL REPORTS, v. 27, n. 3, p. 750+, APR 16 2019. Web of Science Citations: 3.