Identification of subepithelial mesenchymal cells that induce IgA and diversify gut microbiota

Kazuki Nagashima, Shinichiro Sawa, Takeshi Nitta, Masanori Tsutsumi, Tadashi Okamura, Josef M. Penninger, Tomoki Nakashima, Hiroshi Takayanagi

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Immunoglobulin A (IgA) maintains a symbiotic equilibrium with intestinal microbes. IgA induction in the gut-associated lymphoid tissues (GALTs) is dependent on microbial sampling and cellular interaction in the subepithelial dome (SED). However it is unclear how IgA induction is predominantly initiated in the SED. Here we show that previously unrecognized mesenchymal cells in the SED of GALTs regulate bacteria-specific IgA production and diversify the gut microbiota. Mesenchymal cells expressing the cytokine RANKL directly interact with the gut epithelium to control CCL20 expression and microfold (M) cell differentiation. The deletion of mesenchymal RANKL impairs M cell-dependent antigen sampling and B cell-dendritic cell interaction in the SED, which results in a reduction in IgA production and a decrease in microbial diversity. Thus, the subepithelial mesenchymal cells that serve as M cell inducers have a fundamental role in the maintenance of intestinal immune homeostasis.

Original languageEnglish
Pages (from-to)675-682
Number of pages8
JournalNature Immunology
Volume18
Issue number6
DOIs
Publication statusPublished - May 18 2017

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Immunoglobulin A
Lymphoid Tissue
Helper-Inducer T-Lymphocytes
Cell Communication
Dendritic Cells
Cell Differentiation
Homeostasis
B-Lymphocytes
Epithelium
Maintenance
Gastrointestinal Microbiome
Cytokines
Bacteria
Antigens

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Nagashima, K., Sawa, S., Nitta, T., Tsutsumi, M., Okamura, T., Penninger, J. M., ... Takayanagi, H. (2017). Identification of subepithelial mesenchymal cells that induce IgA and diversify gut microbiota. Nature Immunology, 18(6), 675-682. https://doi.org/10.1038/ni.3732

Identification of subepithelial mesenchymal cells that induce IgA and diversify gut microbiota. / Nagashima, Kazuki; Sawa, Shinichiro; Nitta, Takeshi; Tsutsumi, Masanori; Okamura, Tadashi; Penninger, Josef M.; Nakashima, Tomoki; Takayanagi, Hiroshi.

In: Nature Immunology, Vol. 18, No. 6, 18.05.2017, p. 675-682.

Research output: Contribution to journalArticle

Nagashima, K, Sawa, S, Nitta, T, Tsutsumi, M, Okamura, T, Penninger, JM, Nakashima, T & Takayanagi, H 2017, 'Identification of subepithelial mesenchymal cells that induce IgA and diversify gut microbiota', Nature Immunology, vol. 18, no. 6, pp. 675-682. https://doi.org/10.1038/ni.3732
Nagashima, Kazuki ; Sawa, Shinichiro ; Nitta, Takeshi ; Tsutsumi, Masanori ; Okamura, Tadashi ; Penninger, Josef M. ; Nakashima, Tomoki ; Takayanagi, Hiroshi. / Identification of subepithelial mesenchymal cells that induce IgA and diversify gut microbiota. In: Nature Immunology. 2017 ; Vol. 18, No. 6. pp. 675-682.
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