Study of the function of LXRs receptors in the modulation of t CD4 + lymphocytes in vitro and in vivo

• Grant number: 17/23679-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: December 01, 2017
• End date: February 28, 2019
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Pedro Manoel Mendes de Moraes Vieira
• Grantee: Leonardo Pimentel de Freitas
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 15/15626-8 - Macrophages and T lymphocytes immunometabolism in metabolic and inflammatory diseases, AP.JP

Abstract

LXRs (liver X receptors) are nuclear receptors that act as transcription factors and are directly involved in the inflammatory response to various known diseases. However, reports in the literature are not sufficient to elucidate a perfect connection between LXR and inflammation. Therefore, this project was created with the goal of uncovering the role of LXR receptors in the modulation of CD4 + T lymphocytes for Th1, Th2, Th17 and Treg profiles, the latter being anti-inflammatory. Tests will be performed to determine the level of LXR expression in naive and differentiated CD4+ T cells. The results obtained will be important to observe how LXR alpha / beta deficient T cells differentiate in the absence and presence of agonists (T0901317 and GW3965). The efficacy of these agonists will be compared to the endogenous agonist oxysterol, making it possible to determine the specificity of these agonists to LXR. Since several cell types express LXRs, the in vivo tests will bring specific results when using mice that are deficient in LXR alpha/beta only in CD4+ T lymphocytes. The findings of this project aim to increase knowledge about LXRs in the polarization of CD4+ T lymphocytes as well as to obtain the data necessary to present LXR agonists as specific candidates for the potential development of drugs against inflammatory diseases.

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)

DA SILVA, FELIPE CORREA; AGUIAR, CRISTHIANE; PEREIRA, JESSICA A. S.; MONTEIRO, LAUAR DE BRITO; DAVANZO, GUSTAVO GASTAO; CODO, ANA CAMPOS; DE FREITAS, LEONARDO PIMENTEL; BERTI, ALINE SIQUEIRA; FERRUCCI, DANILO LOPES; CASTELUCCI, BIANCA GAZIERI; et al. Ghrelin effects on mitochondrial fitness modulates macrophage function. Free Radical Biology and Medicine, v. 145, p. 61-66, DEC 2019. (17/23679-0, 16/18031-8, 17/12848-5, 18/22505-0, 15/15626-8, 17/00079-7, 17/06225-5)