Langerhans cell-like dendritic cells stimulated with an adjuvant direct the development of Th1 and Th2 cells in vivo.

It is well known that Langerhans cells (LCs) work as the primary orchestrators in the polarization of immune responses towards a T helper type 1 (Th1) or Th2 milieu. In this study, we attempted to generate LCs from murine bone marrow cells and elicit a Th1- or Th2-prone immune response through the LCs after stimulation with Th1 or Th2 adjuvant. LCs were generated from murine bone marrow cells using granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and transforming growth factor (TGF)-β, and were obtained as I-A(d) positive cells. Mice were primed with Th1/Th2 adjuvant- and ovalbumin (OVA)-pulsed LCs and then given a booster injection of OVA 2 days later via the hind footpad. Five days after the OVA injection, the cytokine response in the draining popliteal lymph nodes was investigated by reverse transcription-polymerase chain reaction (RT-PCR) flow cytometry and enzyme-linked immunosorbent assay (ELISA). The generated LCs expressed typical LC surface markers, E-cadherin and Langerin, and were classified accordingly as LC-like dendritic cells (LDCs). Administration of Th1 adjuvant, cytosine-phosphate-guanosine (CpG)-DNA- and OVA-pulsed LDCs into the hind footpads of mice induced a Th1-prone immune response, as represented by up-regulation of IFN-γ production and down-regulation of IL-4 production in the lymph node cells. Conversely, Th2 adjuvant, histamine-pulsed LDCs induced a Th2-prone immune response, as represented by up-regulation of IL-4 production and down-regulation of IFN-γ production. These results suggest that LDCs may be used as a substitute for LCs and have the ability to induce the development of Th1 and Th2 cells in vivo. Our experimental system would therefore be useful for screening of inhibitors of Th1/Th2 differentiation in order to control allergic disease.

Matsui K ，Mori A ，Ikeda R 《-》

Peptidoglycan-induced T helper 2 immune response in mice involves interleukin-10 secretion from Langerhans cells.

Patients with atopic dermatitis (AD) have superficial skin colonization with Staphylococcus aureus and an increased number of T helper (Th)2 cells in their peripheral blood. The purpose of this study was to clarify the involvement of interleukin (IL)-10 secretion from Langerhans cells (LCs) in staphylococcal peptidoglycan (PEG)-induced Th2 immune responses in mice. Mice were primed with LCs pulsed with PEG (or LPS) and ovalbumin (OVA) and then given a booster OVA injection 2 days later in the hind footpad. Five days after the OVA injection, cytokine responses in the draining popliteal lymph nodes were investigated by RT-PCR and ELISA. Production of both IL-10 and IL-12 by cultured LCs was detected by ELISA. Administration of PEG- or LPS-stimulated LCs into the hind footpads of the mice induced Th2-prone and Th1-prone immune responses, respectively, as represented by expression of IL-4 and interferon-γ. In vitro experiments showed that PEG induced greater production of IL-12 p40 from LCs than did LPS, whereas LPS induced greater production of IL-12 p70 from LCs than did PEG. Furthermore, it was found that PEG-stimulated LCs induced greater production of IL-10 than did LPS-stimulated LCs, and that neutralization of IL-10 augmented IL-12 p70 production and inhibited Th2 development by PEG-stimulated LCs. These results suggest that PEG can induce Th2 development through down-regulation of IL-12 p70 production by LCs in an IL-10 production-dependent manner and would explain the role of S. aureus colonization in patients with AD.

Matsui K ，Nishikawa A 《-》

Betamethasone, but Not Tacrolimus, Suppresses the Development of Th2 Cells Mediated by Langerhans Cell-Like Dendritic Cells.

Matsui K ，Tamai S ，Ikeda R 《-》

Effects of Macrolide Antibiotics on Th1 Cell and Th2 Cell Development Mediated by Langerhans Cells.

Matsui K ，Tamai S ，Ikeda R 《JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES》

Effects of anti-allergy drugs on Th1 cell and Th2 cell development mediated by Langerhans cells.

Matsui K ，Shi X ，Komori S ，Higuchi A ... -  《JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES》