Gut-derived acetate promotes B10 cells with antiinflammatory effects

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 acetylcoenzyme 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 bloodderived 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.

Automated summary

Acetate has been shown to promote the differentiation of important immune cells B10 cells, both in mice and human blood cells, by increasing the production of acetylcoenzyme A and promoting posttranslational lysine acetylation. These effects contribute to maintaining immune balance and suggest that delivery of acetate, either directly or through dietary supplementation, could be a promising approach in restoring B10 cells in noncommunicable diseases.