Notch2 signaling is required for proper mast cell distribution and mucosal immunity in the intestine.
Notch receptor-mediated signaling is involved in the developmental process and functional modulation of lymphocytes, as well as in mast cell differentiation. Here, we investigated whether Notch signaling is required for antipathogen host defense regulated by mast cells. Mast cells were rarely found in the small intestine of wild-type C57BL/6 mice but accumulated abnormally in the lamina propria of the small-intestinal mucosa of the Notch2-conditional knockout mice in naive status. When transplanted into mast cell-deficient W(sh)/W(sh) mice, Notch2-null bone marrow-derived mast cells were rarely found within the epithelial layer but abnormally localized to the lamina propria, whereas control bone marrow-derived mast cells were mainly found within the epithelial layer. After the infection of Notch2 knockout and control mice with L3 larvae of Strongyloides venezuelensis, the abundant number of mast cells was rapidly mobilized to the epithelial layer in the control mice. In contrast, mast cells were massively accumulated in the lamina propria of the small intestinal mucosa in Notch2-conditional knockout mice, accompanied by impaired eradication of Strongyloides venezuelensis. These findings indicate that cell-autonomous Notch2 signaling in mast cells is required for proper localization of intestinal mast cells and further imply a critical role of Notch signaling in the host-pathogen interface in the small intestine.
Sakata-Yanagimoto
Mamiko
M
Department of Clinical and Experimental Hematology, University of Tsukuba, Tsukuba, Japan.
Sakai
Toru
T
Miyake
Yasuyuki
Y
Saito
Toshiki I
TI
Maruyama
Haruhiko
H
Morishita
Yasuyuki
Y
Nakagami-Yamaguchi
Etsuko
E
Kumano
Keiki
K
Yagita
Hideo
H
Fukayama
Masashi
M
Ogawa
Seishi
S
Kurokawa
Mineo
M
Yasutomo
Koji
K
Chiba
Shigeru
S
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D001853:Bone Marrow / Q000276:immunology; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D002478:Cells, Cultured; D005260:Female; D019426:Integrases / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000469:parasitology; D007421:Intestine, Small / Q000276:immunology* / Q000469:parasitology; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051883:Receptor, Notch2 / Q000502:physiology*; D013321:Strongyloides / Q000472:pathogenicity; D013322:Strongyloidiasis / Q000276:immunology* / Q000469:parasitology
C497765:Notch2 protein, mouse; D051883:Receptor, Notch2; C045073:Cre recombinase; D019426:Integrases