Mast Cells Modulate Interleukin-4 Production Independently of Interferon-gamma Generation by Invariant Natural Killer T Cells through the Suppression of Notch Signaling

Abstract

The spatial contact of immune cells is predominant machinery for the modulation of local inflammatory sites as much as humoral regulation is for inflammation. In this study, we investigated the role of mast cells in the regulation of invariant natural killer T cells (iNKTs) functions. Co-cultivation of bone-marrow derived mouse mast cells (BMMCs) with purified and stimulated mouse iNKTs caused marked suppression of interleukin (IL)-4 but not interferon (IFN)-γ production in iNKTs. Suppression was accompanied by down-regulation of IL-4 mRNA expression. The Notch intracellular cytoplasmic domain in iNKTs was also completely diminished by co-cultivation with BMMCs. Suppressed IL-4 production was recovered when iNKTs were separately co-cultured with BMMCs using the transwell system. Furthermore, co-culture of iNKTs with activated BMMCs elicited partial suppression of IL-4 production. These findings suggest that mast cells modulate the function of iNKTs via the inhibition of Notch signaling.