The Ets transcription factor Spi-B is essential for the differentiation of intestinal microfold cells

被引:161
作者
Kanaya, Takashi [2 ,3 ]
Hase, Koji [2 ,3 ]
Takahashi, Daisuke [3 ]
Fukuda, Shinji [2 ,3 ]
Hoshino, Katsuaki [1 ,4 ]
Sasaki, Izumi [1 ,4 ,5 ]
Hemmi, Hiroaki [1 ,4 ]
Knoop, Kathryn A. [6 ]
Kumar, Nachiket [6 ]
Sato, Mayuko [7 ]
Katsuno, Tatsuro [8 ]
Yokosuka, Osamu [8 ]
Toyooka, Kiminori [7 ]
Nakai, Kumiko [3 ]
Sakamoto, Ayako [3 ]
Kitahara, Yuuki [3 ,9 ]
Jinnohara, Toshi [2 ,3 ]
McSorley, Stephen J. [10 ]
Kaisho, Tsuneyasu [1 ,4 ,5 ]
Williams, Ifor R. [6 ]
Ohno, Hiroshi [2 ,3 ,9 ]
机构
[1] RIKEN, Res Ctr Allergy & Immunol, Host Def Lab, Kanagawa, Japan
[2] Yokohama City Univ, Grad Sch Nanobiosci, Yokohama, Kanagawa, Japan
[3] RIKEN, Inst Phys & Chem Res, RCAI, Lab Epithelial Immunobiol, Yokohama, Kanagawa, Japan
[4] Osaka Univ, Lab Immune Regulat, World Premier Int Res Ctr Initiat WPI Immunol Fro, Osaka, Japan
[5] Osaka Univ, Grad Sch Med, Dept Allergy & Immunol, Osaka, Japan
[6] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA
[7] RIKEN, Plant Sci Ctr, Yokohama, Kanagawa, Japan
[8] Chiba Univ, Grad Sch Med, Dept Med & Clin Oncol K1, Chiba, Japan
[9] Chiba Univ, Grad Sch Med, Dept Immune Regulat, Chiba, Japan
[10] Univ Calif Davis, Sch Vet Med, Dept Anat Physiol & Cell Biol, Ctr Comparat Med, Davis, CA 95616 USA
基金
美国国家卫生研究院; 日本科学技术振兴机构; 比尔及梅琳达.盖茨基金会; 日本学术振兴会;
关键词
FOLLICLE-ASSOCIATED EPITHELIUM; PEYERS-PATCHES; LYMPHOID FOLLICLES; T-CELLS; STEM-CELLS; MICE; EXPRESSION; INFECTION; PROTEIN; LYMPHOCYTES;
D O I
10.1038/ni.2352
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Intestinal microfold cells (M cells) are an enigmatic lineage of intestinal epithelial cells that initiate mucosal immune responses through the uptake and transcytosis of luminal antigens. The mechanisms of M-cell differentiation are poorly understood, as the rarity of these cells has hampered analysis. Exogenous administration of the cytokine RANKL can synchronously activate M-cell differentiation in mice. Here we show the Ets transcription factor Spi-B was induced early during M-cell differentiation. Absence of Spi-B silenced the expression of various M-cell markers and prevented the differentiation of M cells in mice. The activation of T cells via an oral route was substantially impaired in the intestine of Spi-B-deficient (Spib(-/-)) mice. Our study demonstrates that commitment to the intestinal M-cell lineage requires Spi-B as a candidate master regulator.
引用
收藏
页码:729 / +
页数:10
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