Journal
INTERNATIONAL IMMUNOLOGY
Volume 32, Issue 4, Pages 243-258Publisher
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxz078
Keywords
butyrate; class switch recombination; G-protein-coupled receptor; histone deacetylase; immunoglobulin A
Categories
Funding
- Japanese Society for the promotion of Science or MEXT [JP16H01369, JP17H04089, JP18H04680, JP25293114, JP26116709, JP17K15734]
- Takeda Science Foundation
- NOVARTIS Foundation JAPAN for Promotion of Science
- Yakult Bioscience Foundation
- Keio Gijuku Academic Development Funds
- Asahi Grass Foundation
- Institute of Medical Science, the University of Tokyo
- AMED-Crest [16gm0000000h0101, 17gm1010004h0102, 18gm1010004h0103, 19gm1010004s0104]
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Secretory immunoglobulin A (SIgA), the most abundant antibody isotype in the body, maintains a mutual relationship with commensal bacteria and acts as a primary barrier at the mucosal surface. Colonization by commensal bacteria induces an IgA response, at least partly through a T-cell-independent process. However, the mechanism underlying the commensal-bacteria-induced T-cell-independent IgA response has yet to be fully clarified. Here, we show that commensal-bacteria-derived butyrate promotes T-cell-independent IgA class switching recombination (CSR) in the mouse colon. Notably, the butyrate concentration in human stools correlated positively with the amount of IgA. Butyrate up-regulated the production of transforming growth factor beta 1 and all-trans retinoic acid by CD103(+)CD11b(+) dendritic cells, both of which are critical for T-cell-independent IgA CSR. This effect was mediated by G-protein-coupled receptor 41 (GPR41/FFA3) and GPR109a/HCA2, and the inhibition of histone deacetylase. The butyrate-induced IgA response reinforced the colonic barrier function, preventing systemic bacterial dissemination under inflammatory conditions. These observations demonstrate that commensal-bacteria-derived butyrate contributes to the maintenance of the gut immune homeostasis by facilitating the T-cell-independent IgA response in the colon.
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