Role of sirtuin 1 in CD4+ T cell activation and differentiation in obese transplanted engrafted animals

• Grant number: 17/16711-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: February 01, 2018
• End date: January 31, 2022
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Omar Alberto Domínguez Amorocho
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 19/15411-2 - Role of Sirtuin 1/Sirtuin 3 in response to obesity and aging-associated inflammation, BE.EP.DR

Abstract

Histone Deacetylases (HDACs) are biological molecules responsible for removing acetyl group from lysine residues of histone. Among them, Sirtuin 1 (Sirt1) is identified as an important molecule in cellular metabolism and in immune regulation. The role of Sirt1 in the adaptive immune system is related to cell activation, proliferation and differentiation for different T cell phenotypes. Here, we hypothesize that this role in Th differentiation could be exacerbated in obesity and lead to a stronger immune response against donor antigens. Then, we aim to study the differentiation of Treg and Th1, Th2 and Th17 in normal and obese mice and then to characterize their impact in graft rejection or acceptation in mice where Sirt1 is specifically deleted in CD4+ T cells. SIRT1 floxed mice in CD4+ T cells (SIRT1fl/fl-CD4-Cre) and WT littermates (SIRT1+/+-CD4-cre) will be subjected to a fully skin allograft. Total loss of allograft will be considered as rejection. Effect of Sirt1 on CD4+ T cells will be determined by flow cytometer, western blot, RT-PCR to measure cytokines, transcription factors and activation phenotypes. Differentiation of CD4+ T cell subsets will be done in vitro from naïve cells isolated from CD4+ T cells of SIRT1fl/fl-CD4-Cre and WT littermates. Adoptively transferred Ova-TCR Th cells derived from SIRT1fl/fl-CD4-Cre and WT littermates backcrossed with OT-II mice (Ova-TCR transgenic mice) will be done in CD4 knockout mice and then grafted with ova-expressing skin (transgenic mice expressing ova on keratinocytes). Same parameters will be tested. We expected to unravel the mechanisms behind the role of Sirt1 in alloimmune responses and add new innovative data on this field. (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)

MONTEIRO DE ASSIS, LEONARDO VINICIUS; LACERDA, JOSE THALLES; MORAES, MARIA NATHALIA; DOMINGUEZ-AMOROCHO, OMAR ALBERTO; KINKER, GABRIELA SARTI; MENDES, DAVI; SILVA, MATHEUS MOLINA; MARTINS MENCK, CARLOS FREDERICO; SARAIVA CAMARA, NIELS OLSEN; DE LAURO CASTRUCCI, ANA MARIA. Melanopsin (Opn4) is an oncogene in cutaneous melanoma. COMMUNICATIONS BIOLOGY, v. 5, n. 1, p. 15-pg., 2022-05-13. (19/19435-3, 19/25129-2, 17/24217-0, 17/26651-9, 18/16511-8, 12/50214-4, 18/14728-0, 17/24615-5, 17/18781-0, 20/04524-8, 13/24337-4, 17/16711-4)

FORNI, MARIA FERNANDA; ALBERTO DOMINGUEZ-AMOROCH, OMAR; MONTEIRO DE ASSIS, LEONARDO VINICIUS; KINKER, GABRIELA SARTI; MORAES, MARIA NATHALIA; DE LAURO CASTRUCCI, ANA MARIA; SARAIVA CAMARA, NIELS OLSEN. An Immunometabolic Shift Modulates Cytotoxic Lymphocyte Activation During Melanoma Progression in TRPA1 Channel Null Mice. FRONTIERS IN ONCOLOGY, v. 11, MAY 10 2021. (18/16511-8, 18/14728-0, 17/16711-4, 17/26651-9, 17/24615-5)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

AMOROCHO, Omar Alberto Domínguez. ROLE OF SIRTUIN 1 IN CD4+ T CELLS ACTIVATION AND DIFFERENTIATION IN A MURINE MODEL OF OBESITY AND TRANSPLANTATION. 2022. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.