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

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.

EPITHELIAL cells; IMMUNE response; MUCOUS membranes; TRANSCRIPTION factors; T cells; CELL differentiation; CYTOKINES; LABORATORY mice

Nature Immunology, 2012, Vol 13, Issue 8, p729

1529-2908

Academic Journal

10.1038/ni.2352