The Ets transcription factor Spi-B is essential for the differentiation of intestinal microfold cells.
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.
Laboratory for Epithelial Immunobiology, Research Center for Allergy and Immunology, The Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan.
Takashi
T
Kanaya
Koji
K
Hase
Daisuke
D
Takahashi
Shinji
S
Fukuda
Katsuaki
K
Hoshino
Izumi
I
Sasaki
Hiroaki
H
Hemmi
Kathryn A
KA
Knoop
Nachiket
N
Kumar
Mayuko
M
Sato
Tatsuro
T
Katsuno
Osamu
O
Yokosuka
Kiminori
K
Toyooka
Kumiko
K
Nakai
Ayako
A
Sakamoto
Yuuki
Y
Kitahara
Toshi
T
Jinnohara
Stephen J
SJ
McSorley
Tsuneyasu
T
Kaisho
Ifor R
IR
Williams
Hiroshi
H
Ohno
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D004847:Epithelial Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018928:Immunity, Mucosal / Q000235:genetics; D007413:Intestinal Mucosa / Q000166:cytology* / Q000196:embryology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics* / Q000378:metabolism*; D053245:RANK Ligand / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology
D050783:Proto-Oncogene Proteins c-ets; D053245:RANK Ligand; C514177:Spi-B protein, mouse; C505689:Tnfsf11 protein, mouse