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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