Sox8 is essential for M cell maturation to accelerate IgA response at the early stage after weaning in mice

Shunsuke Kimura, Nobuhide Kobayashi, Yutaka Nakamura, Takashi Kanaya, Daisuke Takahashi, Ryoji Fujiki, Mami Mutoh, Yuuki Obata, Toshihiko Iwanaga, Tomoo Nakagawa, Naoya Kato, Shintaro Sato, Tsuneyasu Kaisho, Hiroshi Ohno, Kouji Hase

Research output: Contribution to journalArticle

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Abstract

Microfold (M) cells residing in the follicle-associated epithelium (FAE) of the gut-associated lymphoid tissue are specialized for antigen uptake to initiate mucosal immune responses. The molecular machinery and biological significance of M cell differentiation, however, remain to be fully elucidated. Here, we demonstrate that Sox8, a member of the SRY-related HMG box transcription factor family, is specifically expressed by M cells in the intestinal epithelium. The expression of Sox8 requires activation of RANKL-RelB signaling. Chromatin immunoprecipitation and luciferase assays revealed that Sox8 directly binds the promoter region of Gp2 to increase Gp2 expression, which is the hallmark of functionally mature M cells. Furthermore, genetic deletion of Sox8 causes a marked decrease in the number of mature M cells, resulting in reduced antigen uptake in Peyer's patches. Consequently, juvenile Sox8-deficient mice showed attenuated germinal center reactions and antigen-specific IgA responses. These findings indicate that Sox8 plays an essential role in the development of M cells to establish mucosal immune responses.

Original languageEnglish
Pages (from-to)831-846
Number of pages16
JournalThe Journal of experimental medicine
Volume216
Issue number4
DOIs
Publication statusPublished - 2019 Apr 1

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Weaning
Immunoglobulin A
Mucosal Immunity
Antigens
Peyer's Patches
Germinal Center
Chromatin Immunoprecipitation
Lymphoid Tissue
Intestinal Mucosa
Luciferases
Genetic Promoter Regions
Cell Differentiation
Transcription Factors
Epithelium

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Sox8 is essential for M cell maturation to accelerate IgA response at the early stage after weaning in mice. / Kimura, Shunsuke; Kobayashi, Nobuhide; Nakamura, Yutaka; Kanaya, Takashi; Takahashi, Daisuke; Fujiki, Ryoji; Mutoh, Mami; Obata, Yuuki; Iwanaga, Toshihiko; Nakagawa, Tomoo; Kato, Naoya; Sato, Shintaro; Kaisho, Tsuneyasu; Ohno, Hiroshi; Hase, Kouji.

In: The Journal of experimental medicine, Vol. 216, No. 4, 01.04.2019, p. 831-846.

Research output: Contribution to journalArticle

Kimura, S, Kobayashi, N, Nakamura, Y, Kanaya, T, Takahashi, D, Fujiki, R, Mutoh, M, Obata, Y, Iwanaga, T, Nakagawa, T, Kato, N, Sato, S, Kaisho, T, Ohno, H & Hase, K 2019, 'Sox8 is essential for M cell maturation to accelerate IgA response at the early stage after weaning in mice', The Journal of experimental medicine, vol. 216, no. 4, pp. 831-846. https://doi.org/10.1084/jem.20181604
Kimura, Shunsuke ; Kobayashi, Nobuhide ; Nakamura, Yutaka ; Kanaya, Takashi ; Takahashi, Daisuke ; Fujiki, Ryoji ; Mutoh, Mami ; Obata, Yuuki ; Iwanaga, Toshihiko ; Nakagawa, Tomoo ; Kato, Naoya ; Sato, Shintaro ; Kaisho, Tsuneyasu ; Ohno, Hiroshi ; Hase, Kouji. / Sox8 is essential for M cell maturation to accelerate IgA response at the early stage after weaning in mice. In: The Journal of experimental medicine. 2019 ; Vol. 216, No. 4. pp. 831-846.
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