International Immunology Advance Access originally published online on October 26, 2006
International Immunology 2006 18(12):1789-1799; doi:10.1093/intimm/dxl113
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IgE-activated mast cells in combination with pro-inflammatory factors induce Th2-promoting dendritic cells
1 Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan
2 Department of Dermatology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan
3 Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan
Correspondence to: N. Kadowaki; E-mail: kadowaki{at}kuhp.kyoto-u.ac.jp
Dendritic cells (DCs) and mast cells (MCs) co-localize in peripheral tissues of antigen entry, i.e. skin and mucosa. Due to the proximity of these two cell types, activation of MCs may affect DC functions. Here, we co-cultured human monocyte-derived DCs with cord blood-derived MCs activated by cross-linking of Fc
RI to elucidate the net effect of the whole MC products on DCs. Activated MCs induced maturation of DCs, and potently suppressed IL-12p70 production by the DCs. Whereas co-culture of DCs with activated MCs alone did not significantly influence the type of CD4+ T cell responses induced by the DCs, DCs co-cultured with activated MCs in the presence of pro-inflammatory or Th1-inducing factors caused Th2 polarization. Although histamine was involved in the induction of DC maturation and Th2 polarization by activated MCs, a combinatorial effect of various MC-derived factors, including those acting in a cell contact-dependent manner, was required for the optimal induction of Th2-promoting DCs. Furthermore, we demonstrated that clusters of DCs are located closely with MCs in lesions of atopic dermatitis. Collectively, this study suggests that the interaction between DCs and IgE-activated MCs in a pro-inflammatory or even Th1-prone environment is instrumental in maintaining and augmenting Th2 responses in allergy, and that disruption of the DC–MC interaction may constitute an effective strategy to treat ongoing allergic diseases.
Keywords: allergy, antigen-presenting cells, human, T cells
Transmitting editor: G. Trinchieri
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