Commensal-bacteria-derived butyrate promotes the t-cell-independent iga response in the colon

Junya Isobe, Shintarou Maeda, Yuuki Obata, Keito Iizuka, Yutaka Nakamura, Yumiko Fujimura, Tatsuki Kimizuka, Kouya Hattori, Yun Gi Kim, Tatsuya Morita, Ikuo Kimura, Stefan Offermanns, Takahiro Adachi, Atsuhito Nakao, Hiroshi Kiyono, Daisuke Takahashi, Koji Hase

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 commensalbacteria-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.

Original languageEnglish
Pages (from-to)243-258
Number of pages16
JournalInternational immunology
Volume32
Issue number4
DOIs
Publication statusPublished - 2020 Apr 1

Keywords

  • Butyrate
  • Class switch recombination
  • G-protein-coupled receptor
  • Histone deacetylase
  • Immunoglobulin a

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Isobe, J., Maeda, S., Obata, Y., Iizuka, K., Nakamura, Y., Fujimura, Y., Kimizuka, T., Hattori, K., Kim, Y. G., Morita, T., Kimura, I., Offermanns, S., Adachi, T., Nakao, A., Kiyono, H., Takahashi, D., & Hase, K. (2020). Commensal-bacteria-derived butyrate promotes the t-cell-independent iga response in the colon. International immunology, 32(4), 243-258. https://doi.org/10.1093/intimm/dxaa078