Evaluation of mTOR on energy metabolism and activation of B cells during experimental intestinal inflammation

• Grant number: 15/26682-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2016
• End date: March 06, 2021
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Paulo José Basso
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 12/02270-2 - New cellular, molecular and immunological mechanisms involved in acute and chronic renal injury: the search for new therapeutical approaches, AP.TEM
• Associated scholarship(s): 18/08563-8 - Nutrients and Metabolism in the regulation of humoral immunity: a role for HIFs, BE.EP.DR

Abstract

B cells functions have been insufficiently studied in the immunopathogenesis of Inflammatory Bowel Diseases (IBD). However, a recent work has indicated substantial importance of B cells to control these intestinal diseases. It is now clear that cellular functions are coordinated by energetic metabolism, which in turn depends on factors such as nutrients and inflammation. Despite this, there are no reports regarding the impact of metabolic changes on B cell activation during the intestinal inflammation. Since the protein kinase mammalian target of rapamycin (mTOR) is one of the most important sensor of intracellular energy status, this project aims to evaluate the role of mTOR on energy metabolism and activation of B cells in experimental colitis induced by dextran sulfate sodium (DSS). In this respect, we assume that B cells activation is related to mTOR signaling pathways, which would be determinant for the inflammation and/or regeneration of intestinal tissue. For this purpose, wild type and transgenic mice (with B cell-specific inactivation or overactivation of mTOR complex 1 - mTORC1) will be exposed to DSS for disease evaluation. The clinical signs, post-mortem score, histologic changes, cytokines and/or antibodies (IgA/IgM) levels, and the immunophenotyping of B cells subpopulations will be also assessed in this context. In addition, the composition and the influence of intestinal microbiota in mTOR activation of B cells will be determined. Considering the metabolic studies, B cells will be evaluated by extracellular flux (seahorse), glucose uptake or cultured without specific nutrients in order to investigate the mTOR activation and its related proteins. Thus, we expect that our results could not only help the understanding of the IBD pathogenesis, but also allow new therapeutic strategies to benefit patients in the future.

Scientific publications

(4)

(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)

VIEIRA, RAQUEL DE SOUZA; CASTOLDI, ANGELA; BASSO, PAULO JOSE; HIYANE, MEIRE IOSHIE; SARAIVA CAMARA, NIELS OLSEN; ALMEIDA, RAFAEL RIBEIRO. Butyrate Attenuates Lung Inflammation by Negatively Modulating Th9 Cells. FRONTIERS IN IMMUNOLOGY, v. 10, JAN 29 2019. (16/03532-1, 15/26682-6, 15/13817-0)

BASSO, PAULO JOSE; SARAIVA CAMARA, NIELS OLSEN; SALES-CAMPOS, HELIOSWILTON. Microbial-Based Therapies in the Treatment of Inflammatory Bowel Disease - An Overview of Human Studies. FRONTIERS IN PHARMACOLOGY, v. 9, JAN 10 2019. (17/05264-7, 15/26682-6)

DE SOUZA BREDA, CRISTIANE NAFFAH; DAVANZO, GUSTAVO GASTAO; BASSO, PAULO JOSE; SARAIVA CAMARA, NIELS OLSEN; MENDES MORAES-VIEIRA, PEDRO MANOEL. Mitochondria as central hub of the immune system. REDOX BIOLOGY, v. 26, SEP 2019. (15/15626-8, 15/26682-6, 14/10910-7, 17/05264-7, 16/18031-8)

BASSO, PAULO JOSE; ANDRADE-OLIVEIRA, VINICIUS; CAMARA, NIELS OLSEN SARAIVA. Targeting immune cell metabolism in kidney diseases. NATURE REVIEWS NEPHROLOGY, v. 17, n. 7, APR 2021. (15/26682-6, 19/14755-0)

Academic Publications

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

BASSO, Paulo José. Evaluation of AMPK and HIF-1α on B cell functions. 2021. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.