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. Conclusion: Dll1/Notch signaling confers the functions as an antigen-presenting cell on mast cells, which preferentially induce the differentiation of TH2. (J Allergy Clin Immunol 2009;123:74-81.)