Evaluating the role of the short-chain fatty acids receptor GPR43 in the regulation of central nervous system autoimmunity by gut microbiota

• Main Authors: Prado - Terrazas, Carolina
• Other Authors: Fundación Ciencia Para La Vida
• Format: Report
• Language: unknown
• Published: 2023
• Subjects: short-chain fatty acids microbiome autoimmunity; Biologia Celular; Magallanes; Valparaíso; Bío Bío; General Bernardo O'Higgins; Antártica
• Online Access: https://hdl.handle.net/10533/48536

2 To determine the local and systemic levels of SCFAs during the time-course of EAE. TOTAL This objective was totally accomplished, and with results that led us to investigate deeper into the mechanism. First, the analysis of the feces and serum of mice during the development of this autoimmunity allowed us to determine that prior to the appearance of clinical symptoms there is a systemic decrease in acetate, while at the peak of the disease a decrease in propionate was observed in the colonic mucosa. The results of objectives 1 and 2 indicated that during this autoimmune disease there is a reduced signaling via GPR43 in the lymphocytes of the intestinal mucosa. Additional experiments indicated that there is an accumulation of T lymphocytes in the intestinal mucosa in the colon of mice with EAE, and that as a result of reduced signaling via GPR43, these cells migrate to the central nervous system by a mechanism that involves CXCR3 chemokine receptor-mediated migration. 3 To evaluate how GPR43-signaling in the lymphoid compartment affects the acquisition of pro- and anti-inflammatory phenotypes in vitro. TOTAL This objective was fully accomplished, with significant statistical differences and consistent with the in vivo results. The contribution of GPR43 signaling to the phenotypic changes observed in colonic mucosal T lymphocytes during this autoimmunity was determined. Through the use of specific GPR43 agonists and natural agonists in in vitro cultures, it was concluded that stimulation of the GPR43 receptor promotes an anti-inflammatory profile in intestinal mucosal lymphocytes. This results strongly suggests a suppressor potential of these cells for the treatment of autoimmune diseases and gave the basis for the experiments of the next objectives. 4 To assess how GPR43 expressed in the lymphoid compartment affect the development of EAE TOTAL This objective was fully accomplished and involved a change in the proposed methodology. To study the effect of GPR43 exclusively in the lymphocyte compartment and ...