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

Takashi Kanaya; Koji Hase; Daisuke Takahashi; Shinji Fukuda; Katsuaki Hoshino; Izumi Sasaki; Hiroaki Hemmi; Kathryn A. Knoop; Nachiket Kumar; Mayuko Sato; Tatsuro Katsuno; Osamu Yokosuka; Kiminori Toyooka; Kumiko Nakai; Ayako Sakamoto; Yuuki Kitahara; Toshi Jinnohara; Stephen J. Mcsorley; Tsuneyasu Kaisho; Ifor R. Williams; Hiroshi Ohno

doi:10.1038/ni.2352

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

Takashi Kanaya, Koji Hase, Daisuke Takahashi, Shinji Fukuda, Katsuaki Hoshino, Izumi Sasaki, Hiroaki Hemmi, Kathryn A. Knoop, Nachiket Kumar, Mayuko Sato, Tatsuro Katsuno, Osamu Yokosuka, Kiminori Toyooka, Kumiko Nakai, Ayako Sakamoto, Yuuki Kitahara, Toshi Jinnohara, Stephen J. Mcsorley, Tsuneyasu Kaisho, Ifor R. WilliamsHiroshi Ohno

Immunology

Research output: Contribution to journal › Article › peer-review

131 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	729-736
Number of pages	8
Journal	Nature immunology
Volume	13
Issue number	8
DOIs	https://doi.org/10.1038/ni.2352
State	Published - Aug 2012

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1038/ni.2352

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Kanaya, T., Hase, K., Takahashi, D., Fukuda, S., Hoshino, K., Sasaki, I., Hemmi, H., Knoop, K. A., Kumar, N., Sato, M., Katsuno, T., Yokosuka, O., Toyooka, K., Nakai, K., Sakamoto, A., Kitahara, Y., Jinnohara, T., Mcsorley, S. J., Kaisho, T., ... Ohno, H. (2012). The Ets transcription factor Spi-B is essential for the differentiation of intestinal microfold cells. Nature immunology, 13(8), 729-736. https://doi.org/10.1038/ni.2352

Kanaya, T, Hase, K, Takahashi, D, Fukuda, S, Hoshino, K, Sasaki, I, Hemmi, H, Knoop, KA, Kumar, N, Sato, M, Katsuno, T, Yokosuka, O, Toyooka, K, Nakai, K, Sakamoto, A, Kitahara, Y, Jinnohara, T, Mcsorley, SJ, Kaisho, T, Williams, IR & Ohno, H 2012, 'The Ets transcription factor Spi-B is essential for the differentiation of intestinal microfold cells', Nature immunology, vol. 13, no. 8, pp. 729-736. https://doi.org/10.1038/ni.2352

@article{6253fd07f0564c2ca4d2a62cb9a89a1f,

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

abstract = "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.",

author = "Takashi Kanaya and Koji Hase and Daisuke Takahashi and Shinji Fukuda and Katsuaki Hoshino and Izumi Sasaki and Hiroaki Hemmi and Knoop, {Kathryn A.} and Nachiket Kumar and Mayuko Sato and Tatsuro Katsuno and Osamu Yokosuka and Kiminori Toyooka and Kumiko Nakai and Ayako Sakamoto and Yuuki Kitahara and Toshi Jinnohara and Mcsorley, {Stephen J.} and Tsuneyasu Kaisho and Williams, {Ifor R.} and Hiroshi Ohno",

note = "Funding Information: We thank Z. Guo, Y. Obata, Y. Oohara, Y. Fujimura, M. Ohmae, C. Uetake, Y. Usami and S. Kimura for technical support; T. Kawai for electron microscopy analysis; and H. Matsui (Kitasato University) for S. Typhimurium. Supported by RIKEN (T.Kan., D.T. and I.S.), the Kishimoto Foundation (K.Ho., I.S., H.H. and T.Kai.), the Ministry of Education, Culture, Sports, Science and Technology of Japan (21022049 to K.Ha.; 20060033, 21022048 and 21117003 to T.Kai.; and 20113003 to H.O.), the Japan Society for the Promotion of Science (22689017 to K.Ha.; 23790550 to T.Kan.; 21390155 to H.O.; and 20390146, 23390124 and 18590483 to T.Kai.), the Japan Science and Technology Agency (K.Ha.), The Japan Science Society (K.Ha.), The Takeda Science Foundation (H.O.), The Mitsubishi Foundation (H.O.), The Uehara Memorial Foundation (T.Kai.), the US National Institutes of Health (DK64730 to I.R.W.) and the Bill & Melinda Gates Foundation (OPP1006977 to I.R.W.).",

year = "2012",

month = aug,

doi = "10.1038/ni.2352",

language = "English (US)",

volume = "13",

pages = "729--736",

journal = "Nature Immunology",

issn = "1529-2908",

publisher = "Nature Publishing Group",

number = "8",

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TY - JOUR

T1 - The Ets transcription factor Spi-B is essential for the differentiation of intestinal microfold cells

AU - Kanaya, Takashi

AU - Hase, Koji

AU - Takahashi, Daisuke

AU - Fukuda, Shinji

AU - Hoshino, Katsuaki

AU - Sasaki, Izumi

AU - Hemmi, Hiroaki

AU - Knoop, Kathryn A.

AU - Kumar, Nachiket

AU - Sato, Mayuko

AU - Katsuno, Tatsuro

AU - Yokosuka, Osamu

AU - Toyooka, Kiminori

AU - Nakai, Kumiko

AU - Sakamoto, Ayako

AU - Kitahara, Yuuki

AU - Jinnohara, Toshi

AU - Mcsorley, Stephen J.

AU - Kaisho, Tsuneyasu

AU - Williams, Ifor R.

AU - Ohno, Hiroshi

N1 - Funding Information: We thank Z. Guo, Y. Obata, Y. Oohara, Y. Fujimura, M. Ohmae, C. Uetake, Y. Usami and S. Kimura for technical support; T. Kawai for electron microscopy analysis; and H. Matsui (Kitasato University) for S. Typhimurium. Supported by RIKEN (T.Kan., D.T. and I.S.), the Kishimoto Foundation (K.Ho., I.S., H.H. and T.Kai.), the Ministry of Education, Culture, Sports, Science and Technology of Japan (21022049 to K.Ha.; 20060033, 21022048 and 21117003 to T.Kai.; and 20113003 to H.O.), the Japan Society for the Promotion of Science (22689017 to K.Ha.; 23790550 to T.Kan.; 21390155 to H.O.; and 20390146, 23390124 and 18590483 to T.Kai.), the Japan Science and Technology Agency (K.Ha.), The Japan Science Society (K.Ha.), The Takeda Science Foundation (H.O.), The Mitsubishi Foundation (H.O.), The Uehara Memorial Foundation (T.Kai.), the US National Institutes of Health (DK64730 to I.R.W.) and the Bill & Melinda Gates Foundation (OPP1006977 to I.R.W.).

PY - 2012/8

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N2 - 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.

AB - 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.

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JO - Nature Immunology

JF - Nature Immunology

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

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