Identification of specific gene expression profiles in human mast cells mediated by Toll-like receptor 4 and FcepsilonRI.
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 gamma (IFN-gamma). To systematically explore how human MCs modulate the immune system following TLR4-mediated activation and FcepsilonRI 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-gamma, 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 pathogen- and antigen-specific immune responses and that human MCs may play important roles in innate and adaptive immunity.
Okumura
Shigeru
S
Laboratory of Allergy Transcriptome, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Japan.
Kashiwakura
Jun-ichi
J
Tomita
Hisashi
H
Matsumoto
Kenji
K
Nakajima
Toshiharu
T
Saito
Hirohisa
H
Okayama
Yoshimichi
Y
D054402:Chemokine CCL1; D019742:Chemokines, CC / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D015848:Interleukin-5 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000166:cytology; D008407:Mast Cells / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D017455:Receptors, IgE / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
C065971:CCL1 protein, human; D054402:Chemokine CCL1; D019742:Chemokines, CC; D015848:Interleukin-5; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D017455:Receptors, IgE; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha