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Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2002-12-3929.
Submitted December 27, 2002
Accepted June 10, 2003
Identification of specific gene expression profile in human mast cells via Toll-like receptor 4 and Fc RI
Shigeru Okumura, Jun-ichi Kashiwakura, Hisashi Tomita, Kenji Matsumoto, Toshiharu Nakajima, Hirohisa Saito, and Yoshimichi Okayama*
Laboratory for Allergy Transcriptome, Research Center for Allergy & Immunology, RIKEN Yokohama Institute, Yokohama, Japan
Department of Allergy & Immunology, National Research Institute for Child Health and Development, Tokyo, Japan
Department of Microbiology, Tokyo Dental College, Chiba, Japan
* Corresponding author; email: yokayama{at}nch.go.jp.
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 LPS- or 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 to 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 pathogen- and antigen-specific immune responses and that human MCs may play important roles in innate and adaptive immunity.
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