Commensal-bacteria-derived butyrate promotes the T-cell-independent IgA response in the colon

• Published in: International immunology Vol. 32; no. 4; pp. 243 - 258
• Main Authors: Isobe, Junya, Maeda, Shintarou, Obata, Yuuki, Iizuka, Keito, Nakamura, Yutaka, Fujimura, Yumiko, Kimizuka, Tatsuki, Hattori, Kouya, Kim, Yun-Gi, Morita, Tatsuya, Kimura, Ikuo, Offermanns, Stefan, Adachi, Takahiro, Nakao, Atsuhito, Kiyono, Hiroshi, Takahashi, Daisuke, Hase, Koji
• Format: Journal Article
• Language: English
• Published: UK Oxford University Press 12-04-2020
• Subjects: immunoglobulin A; butyrate; class switch recombination; histone deacetylase; G-protein-coupled receptor
• ISSN: 1460-2377; 1460-2377
• DOI: 10.1093/intimm/dxz078

Abstract
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 β1 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.
Butyrate conditions DCs to promote IgA production in the gut