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

Anatomy, Physiology and Cell Biology

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

128 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

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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

The Ets transcription factor Spi-B is essential for the differentiation of intestinal microfold cells. / Kanaya, Takashi; Hase, Koji; Takahashi, Daisuke; Fukuda, Shinji; Hoshino, Katsuaki; Sasaki, Izumi; Hemmi, Hiroaki; Knoop, Kathryn A.; Kumar, Nachiket; Sato, Mayuko; Katsuno, Tatsuro; Yokosuka, Osamu; Toyooka, Kiminori; Nakai, Kumiko; Sakamoto, Ayako; Kitahara, Yuuki; Jinnohara, Toshi; Mcsorley, Stephen J; Kaisho, Tsuneyasu; Williams, Ifor R.; Ohno, Hiroshi.

In: Nature Immunology, Vol. 13, No. 8, 08.2012, p. 729-736.

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

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

Kanaya, Takashi ; Hase, Koji ; Takahashi, Daisuke ; Fukuda, Shinji ; Hoshino, Katsuaki ; Sasaki, Izumi ; Hemmi, Hiroaki ; Knoop, Kathryn A. ; Kumar, Nachiket ; Sato, Mayuko ; Katsuno, Tatsuro ; Yokosuka, Osamu ; Toyooka, Kiminori ; Nakai, Kumiko ; Sakamoto, Ayako ; Kitahara, Yuuki ; Jinnohara, Toshi ; Mcsorley, Stephen J ; Kaisho, Tsuneyasu ; Williams, Ifor R. ; Ohno, Hiroshi. / The Ets transcription factor Spi-B is essential for the differentiation of intestinal microfold cells. In: Nature Immunology. 2012 ; Vol. 13, No. 8. pp. 729-736.

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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.",

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