Gut-derived acetate promotes B10 cells with antiinflammatory effects

JCI Insight. 2021 Apr 8;6(7):e144156. doi: 10.1172/jci.insight.144156.

Abstract

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.

Keywords: Beta cells; Immunology; Metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / blood
  • Acetates / metabolism*
  • Acetates / pharmacology*
  • Acetyl Coenzyme A / metabolism
  • Acetylation
  • Animals
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / therapy*
  • B-Lymphocytes, Regulatory / drug effects*
  • B-Lymphocytes, Regulatory / physiology
  • B-Lymphocytes, Regulatory / transplantation
  • Cell Differentiation / drug effects
  • Dietary Fiber / pharmacology*
  • Fatty Acids, Volatile / metabolism
  • Fatty Acids, Volatile / pharmacology
  • Female
  • Humans
  • Interleukin-10
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Neutrophils / cytology
  • Neutrophils / drug effects
  • Receptors, G-Protein-Coupled / genetics

Substances

  • Acetates
  • Dietary Fiber
  • Fatty Acids, Volatile
  • Ffar2 protein, mouse
  • IL10 protein, mouse
  • Receptors, G-Protein-Coupled
  • Interleukin-10
  • Acetyl Coenzyme A