title: Peptidoglycan-induced T helper 2 immune response in mice involves interleukin-10 secretion from Langerhans cells.
abstract: 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.
authors.affiliation: Department of Immunobiology, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan. kmatsui@my‐pharm.ac.jp
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Matsui
authors.forename: Akemi
authors.initials: A
authors.lastname: Nishikawa
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010457:Peptidoglycan / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013211:Staphylococcus aureus / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: C556062:IL10 protein, mouse; D010457:Peptidoglycan; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma