TY - JOUR
T1 - Commensal-bacteria-derived butyrate promotes the t-cell-independent iga response in the colon
AU - Isobe, Junya
AU - Maeda, Shintarou
AU - Obata, Yuuki
AU - Iizuka, Keito
AU - Nakamura, Yutaka
AU - Fujimura, Yumiko
AU - Kimizuka, Tatsuki
AU - Hattori, Kouya
AU - Kim, Yun Gi
AU - Morita, Tatsuya
AU - Kimura, Ikuo
AU - Offermanns, Stefan
AU - Adachi, Takahiro
AU - Nakao, Atsuhito
AU - Kiyono, Hiroshi
AU - Takahashi, Daisuke
AU - Hase, Koji
N1 - Funding Information:
This work was supported by Japanese Society for the promotion of Science or MEXT Grants-in-Aid for Scientific Research JP16H01369, JP17H04089, JP18H04680, JP25293114, JP26116709 (K.H.) and JP17K15734 (D.T.); AMED-Crest 16gm0000000h0101, 17gm1010004h0102, 18gm1010004h0103, 19gm1010004s0104 (K.H.), and. This study was also supported by grants from the Takeda Science Foundation (K.H. and D.T.), the NOVARTIS Foundation JAPAN for Promotion of Science (K.H.), Yakult Bioscience Foundation (K.H.), Keio Gijuku Academic Development Funds (K.H.), the Asahi Grass Foundation (K.H.) and the Grant for Joint Research Project of the Institute of Medical Science, the University of Tokyo (K.H.).
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
KW - Butyrate
KW - Class switch recombination
KW - G-protein-coupled receptor
KW - Histone deacetylase
KW - Immunoglobulin a
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U2 - 10.1093/intimm/dxaa078
DO - 10.1093/intimm/dxaa078
M3 - Article
C2 - 31858119
AN - SCOPUS:85083623542
VL - 32
SP - 243
EP - 258
JO - International Immunology
JF - International Immunology
SN - 0953-8178
IS - 4
ER -