Notch signaling confers antigen-presenting cell functions on mast cells.
BACKGROUND
Notch signaling is involved in cell fate determination along with the development of the immune system. However, very little is known about the role for Notch signaling in mast cells.


OBJECTIVE
We investigated the role of Notch signaling in mast cell functions.


METHODS
After mouse bone marrow-derived mast cells (BMMCs) or peritoneal mast cells (PMCs) were cocultured with mouse Notch ligand-expressing chinese hamster ovary cells for 5 days, we examined the mast cell surface expressions of MHC-II molecules and OX40 ligand (OX40L), Fc epsilon RI-mediated cytokine production, and the effects of the mast cells on proliferation and differentiation of naive CD4(+) T cells in vitro.


RESULTS
We showed that BMMCs and PMCs constitutively expressed Notch1 and Notch2 proteins on the cell surface. We also found that Delta-like 1 (Dll1)/Notch signaling induced the expression of MHC-II and upregulated the expression level of OX40L on the surface of the mast cells. Dll1/Notch signaling augmented Fc epsilon RI-mediated IL-4, IL-6, IL-13, and TNF production by BMMCs. Dll1-stimulated MHC-II(+)OX40L(high) BMMCs promoted proliferation of naive CD4(+) T cells and their differentiation into T(H)2 cells producing IL-4, IL-5, IL-10, and IL-13.


CONCLUSIONS
Dll1/Notch signaling confers the functions as an antigen-presenting cell on mast cells, which preferentially induce the differentiation of T(H)2.
Nakano
Nobuhiro
N
Atopy (Allergy) Research Center, Juntendo University School of Medicine, Tokyo, Japan. nbnakano@med.juntendo.ac.jp
Nishiyama
Chiharu
C
Yagita
Hideo
H
Koyanagi
Akemi
A
Akiba
Hisaya
H
Chiba
Shigeru
S
Ogawa
Hideoki
H
Okumura
Ko
K
D000818:Animals; D030801:Animals, Genetically Modified; D000938:Antigen-Presenting Cells; D016466:CHO Cells; D002135:Calcium-Binding Proteins; D049109:Cell Proliferation; D018920:Coculture Techniques; D006224:Cricetinae; D003412:Cricetulus; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D008407:Mast Cells / Q000166:cytology / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D053278:OX40 Ligand; D051881:Receptor, Notch1 / Q000235:genetics / Q000276:immunology*; D051883:Receptor, Notch2 / Q000235:genetics / Q000276:immunology*; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D002135:Calcium-Binding Proteins; D016207:Cytokines; C512925:Dlk1 protein, mouse; D000949:Histocompatibility Antigens Class II; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C497762:Notch1 protein, mouse; C497765:Notch2 protein, mouse; D053278:OX40 Ligand; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D017455:Receptors, IgE; C504586:Tnfsf4 protein, mouse; D048069:Tumor Necrosis Factors