Identification of specific gene expression profiles in human mast cells mediated by Toll-like receptor 4 and Fc RI

Rodent mast cells (MCs) are reported to play a pivotal role in both innate and adaptive immunity. However, there is so far no evidence that human MCs are involved in innate immunity. We found that a functional Toll-like receptor 4 (TLR4) was expressed on human MCs when it was up-regulated by interferon (IFN). To systematically explore how human MCs modulate the immune system following TLR4-mediated activation and Fc RI aggregation, we used high-density oligonucleotide probe arrays (GeneChip) to compare the lipopolysaccharide (LPS)– induced gene expression profile with the IgE/anti-IgE–mediated profile in MCs. Both a shared core response, and LPSor anti-IgE–specific programs of gene expression were observed in MCs. Furthermore, MCs exhibited an antiviral response gene program in response to IFN, and LPS sustained that expression. Compared with the LPS-stimulated gene expression profile of human peripheral blood mononuclear cells, LPS-stimulated MCs specifically induced a subset of genes that included a Th2 cytokine and chemokines that recruit Th2 cells and eosinophils. These results reveal that human MCs express tailored pathogenand antigen-specific immune responses and that human MCs may play important roles in innate and adaptive immunity. (Blood. 2003;102:2547-2554)