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J Exp Med. 2019 Apr 1;216(4):831-846. doi: 10.1084/jem.20181604. Epub 2019 Mar 15.

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

Author information

1
Laboratory of Histology and Cytology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan skimu@med.hokudai.ac.jp.
2
Division of Biochemistry, Faculty of Pharmacy, Keio University, Tokyo, Japan.
3
Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.
4
Division of Immunobiology, Department of Medical Life Science, Graduate School of Medical Life Science, Yokohama City University, Kanagawa, Japan.
5
Department of Applied Genomics, Kazusa DNA Research Institute, Kisarazu, Japan.
6
Department of Orthodontics, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
7
Laboratory of Histology and Cytology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
8
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.
9
Mucosal Vaccine Project, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
10
Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan.
11
Division of Biochemistry, Faculty of Pharmacy, Keio University, Tokyo, Japan hase-kj@pha.keio.ac.jp.

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.

PMID:
30877171
PMCID:
PMC6446867
[Available on 2019-10-01]
DOI:
10.1084/jem.20181604

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