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

Grant number: 15/26682-6
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2016
Effective date (End): March 06, 2021
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal researcher:Niels Olsen Saraiva Câmara
Grantee:Paulo José Basso
Home 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.

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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)
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. Web of Science Citations: 0.
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. Web of Science Citations: 4.
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. Web of Science Citations: 3.
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. Web of Science Citations: 10.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.