Epithelial-stromal interaction via Notch signaling is essential for the full maturation of gut-associated lymphoid tissues.
Intrinsic Notch signaling in intestinal epithelial cells restricts secretory cell differentiation. In gut-associated lymphoid tissue (GALT), stromal cells located beneath the follicle-associated epithelium (FAE) abundantly express the Notch ligand delta-like 1 (Dll1). Here, we show that mice lacking Rbpj-a gene encoding a transcription factor implicated in Notch signaling-in intestinal epithelial cells have defective GALT maturation. This defect can be attributed to the expansion of goblet cells, which leads to the down-regulation of CCL20 in FAE. These data demonstrate that epithelial Notch signaling maintained by stromal cells contributes to the full maturation of GALT by restricting secretory cell differentiation in FAE.
Division of Mucosal Barriology, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan Department of Immune Regulation, Graduate School of Medical and Pharmaceutical Sciences Chiba University, Chiba, Japan Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Yuuki
Y
Obata
Laboratory of Histology and Cytology, Graduate School of Medicine Hokkaido University, Sapporo, Japan.
Shunsuke
S
Kimura
Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Gaku
G
Nakato
Department of Biochemistry, Faculty of Pharmacy, Keio University, Tokyo, Japan.
Keito
K
Iizuka
Department of Biochemistry, Faculty of Pharmacy, Keio University, Tokyo, Japan.
Yurika
Y
Miyagawa
Division of Mucosal Barriology, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Yutaka
Y
Nakamura
Division of Mucosal Barriology, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan Department of Biochemistry, Faculty of Pharmacy, Keio University, Tokyo, Japan.
Yukihiro
Y
Furusawa
Laboratory for Immunogenetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Machiko
M
Sugiyama
AK Project, Graduate School of Medicine Kyoto University, Kyoto, Japan.
Keiichiro
K
Suzuki
Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Masashi
M
Ebisawa
Division of Mucosal Barriology, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan Department of Biochemistry, Faculty of Pharmacy, Keio University, Tokyo, Japan.
Yumiko
Y
Fujimura
Laboratory for Immunogenetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Hisahiro
H
Yoshida
Laboratory of Histology and Cytology, Graduate School of Medicine Hokkaido University, Sapporo, Japan.
Toshihiko
T
Iwanaga
Division of Mucosal Barriology, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan Department of Biochemistry, Faculty of Pharmacy, Keio University, Tokyo, Japan PRESTO, Japan Science and Technology Agency, Tokyo, Japan hase-kj@pha.keio.ac.jp hiroshi.ohno@riken.jp.
Koji
K
Hase
Department of Immune Regulation, Graduate School of Medical and Pharmaceutical Sciences Chiba University, Chiba, Japan Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan hase-kj@pha.keio.ac.jp hiroshi.ohno@riken.jp.
Hiroshi
H
Ohno
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism
D051880:Receptors, Notch
Notch signaling; follicle‐associated epithelium; gut‐associated lymphoid tissues; intestinal epithelial cells