Gut-derived acetate promotes B10 cells with antiinflammatory effects
C.I. Daïen, J. Tan, R. Audo, J. Mielle, L.E. Quek, J.R. Krycer, A. Angelatos, M. Duraes, G. Pinget, D. Ni, R. Robert, M.J. Alam, M.C.B. Amian, F. Sierro, A. Parmar, G. Perkins, S. Hoque, A.K. Gosby, S.J. Simpson, R.V. Ribeiro, C.R. Mackay, L. Macia
C.I. Daïen, J. Tan, R. Audo, J. Mielle, L.E. Quek, J.R. Krycer, A. Angelatos, M. Duraes, G. Pinget, D. Ni, R. Robert, M.J. Alam, M.C.B. Amian, F. Sierro, A. Parmar, G. Perkins, S. Hoque, A.K. Gosby, S.J. Simpson, R.V. Ribeiro, C.R. Mackay, L. Macia
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Research Article Immunology Metabolism

Gut-derived acetate promotes B10 cells with antiinflammatory effects

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.

Authors

C.I. Daïen, J. Tan, R. Audo, J. Mielle, L.E. Quek, J.R. Krycer, A. Angelatos, M. Duraes, G. Pinget, D. Ni, R. Robert, M.J. Alam, M.C.B. Amian, F. Sierro, A. Parmar, G. Perkins, S. Hoque, A.K. Gosby, S.J. Simpson, R.V. Ribeiro, C.R. Mackay, L. Macia

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Figure 2

Acetate-induced B10 cells are functional in vitro and in vivo.

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Acetate-induced B10 cells are functional in vitro and in vivo. (A) The p...
(A) The proportion of IL-10+ cells was assessed among purified peritoneal B cells by flow cytometry. Cells were either unstimulated or incubated overnight with 10 mM acetate (Ace) (from n = 8 mice per group). (B) IL-10 quantification by ELISA in supernatants of purified B cells incubated overnight with 10 mM acetate (n = 6 per group). (C) Collagen antibody induced arthritis was induced by injecting i.p 4 mg anticollagen monoclonal antibodies on day 0 and 50 μg LPS on day 3. 106 of nonstimulated (B-NS) or overnight stimulated peritoneal B cells with 10 mM acetate only (B-Ace) were injected i.p 2 hours after anticollagen antibody injection. Joints were monitored for 7 days and (D) collected for histological analysis (n = 7–9 per group). Increased cellular infiltrated, hyperplasia, and pannus formation (indicated by i–iii, respectively) were seen in B-NS groups compared with B-Ace groups (scale bar: 100 μm). (E) The proportion of splenic CD4+CD25+FoxP3+ Tregs was assessed by flow cytometry. Means and SEM are presented. Two-way ANOVA was performed and Wilcoxon paired tests for 2-group comparisons with *P < 0.05 and **P < 0.01. Un, unstimulated.