RESUMEN
Autoimmune diseases are characterized by a breakdown of immune tolerance partly due to environmental factors. The short-chain fatty acid acetate, derived mostly from gut microbial fermentation of dietary fiber, promotes antiinflammatory Tregs and protects mice from type 1 diabetes, colitis, and allergies. Here, we show that the effects of acetate extend to another important immune subset involved in tolerance, the IL-10-producing regulatory B cells (B10 cells). Acetate directly promoted B10 cell differentiation from mouse B1a cells both in vivo and in vitro. These effects were linked to metabolic changes through the increased production of acetyl-coenzyme A, which fueled the TCA cycle and promoted posttranslational lysine acetylation. Acetate also promoted B10 cells from human blood cells through similar mechanisms. Finally, we identified that dietary fiber supplementation in healthy individuals was associated with increased blood-derived B10 cells. Direct delivery of acetate or indirect delivery via diets or bacteria that produce acetate might be a promising approach to restore B10 cells in noncommunicable diseases.
Asunto(s)
Acetatos/metabolismo , Acetatos/farmacología , Artritis Experimental/terapia , Linfocitos B Reguladores/efectos de los fármacos , Fibras de la Dieta/farmacología , Acetatos/sangre , Acetilcoenzima A/metabolismo , Acetilación , Animales , Artritis Experimental/inmunología , Linfocitos B Reguladores/fisiología , Linfocitos B Reguladores/trasplante , Diferenciación Celular/efectos de los fármacos , Ácidos Grasos Volátiles/metabolismo , Ácidos Grasos Volátiles/farmacología , Femenino , Humanos , Interleucina-10 , Masculino , Ratones Endogámicos C57BL , Ratones Mutantes , Neutrófilos/citología , Neutrófilos/efectos de los fármacos , Receptores Acoplados a Proteínas G/genéticaRESUMEN
Mortality in rheumatoid arthritis (RA) is doubled when compared to the general population. This excess in mortality can be explained in half of cases by cardiovascular (CV) events. The risk of myocardial infarction is increased by about 60% in RA. Mortality secondary to cerebrovascular stroke is increased by 50% even if the incidence of stroke is not increased. Indeed, the risk of fatal CV events is increased in RA when compared to the general population. The increased CV risk cannot be explained only by traditional CV risk factors, even if smoking and changes in lipid profile may be implied. It is mainly related to the chronic inflammatory condition that causes many metabolic disturbances. Other parameters such as treatments used in RA also play a role. Thus, it is essential for proper management of RA patients to be aware of this risk and to treat any modifiable CV risk factors.
