The role of mTOR signaling pathway in the differentiation, activation and polarization of short chain fatty acid-induced CD4+ t lymphocytes

Abstract

Short Chain Fatty Acids (SCFA) are end-products produced from the fermentation of complex carbohydrates by intestinal microbiota. It has been reported that AGCCs have anti-inflammatory properties, protecting from colitis as well as acting in modulation of neutrophil's function and in the maturation and activation of dendritic cells. However, their role in the function of T CD4 + cells, crucial in the course of the immune response, has not been investigated. The mTOR pathway and its components mTORC1 and mTORC2 complexes, has been regarded as a central pathway in the regulation of cellular metabolism, because they can sense the extracellular environment and be activated depending on the availability of elements important for cellular metabolism, such as amino acids. Although broadly studied, it is not fully elucidated which components can activate this pathway. Preliminary data generated in my PhD shows that in the presence of SCFA there is a greater differentiation of CD4 + T regulatory cells (Foxp3 +) and IL-17-producing cells (Th17). This project aims to evaluate the role of SCFAs in the differentiation of CD4 + T lymphocytes in Th17, Treg, Th1 and Th2 cells in vitro, and also verify the participation of the mTOR and its two complexes mTORC1 and mTORC2 in this context. We believe that this study will bring innovative results regarding the understanding of the regulation of the mTOR pathway activation and the role of SCFAs in the biology of the CD4 + T cells subtypes. (AU)