title: Percutaneous application of peptidoglycan from Staphylococcus aureus induces infiltration of CCR4+ cells into mouse skin.
abstract: BACKGROUND
  The lesional skin of patients with atopic dermatitis has an increased number of type 2 helper T (TH2) cells in the dermis and is superficially colonized by Staphylococcus aureus. The purpose of this study was to determine the effects of peptidoglycan (PEG) from S aureus on TH2 cell induction in murine skin.
  
  
  METHODS
  Mice were sensitized with house dust mite antigen (MA) by topical application to barrier-disrupted abdominal skin. Seven days after sensitization, PEG was applied to the barrier-disrupted dorsal skin. After a further 3 days, C-C chemokine receptor type 4-positive (CCR4+) cells were counted in the PEG-treated skin.The production of chemokine (C-C) motif ligand 17 (CCL17) (thymus- and activation-regulated chemokine) and CCL22 (macrophage-derived chemokine) in the skin was investigated using reverse transcriptase polymerase chain reaction and immunohistological analysis.
  
  
  RESULTS
  Application of PEG to the dorsal skin of MA-sensitized mice led to a significant increase in the number of cells expressing CCR4 in the dermis. The skin of PEG-treated mice showed an increased level of CCL17 mRNA expression, which coincided with TH2 cytokine mRNA expression. Immunohistological analysis demonstrated that levels of CCL17 transcripts corresponded to those of protein synthesis in the epidermis. CCL17 production was induced mainly by Langerhans cells stimulated with PEG. Furthermore, intraperitoneal injection of anti-CCL17 antibody abrogated the induction of CCR4+ cells in the skin.
  
  
  CONCLUSIONS
  These results suggest that PEG may induce TH2 cells in the skin through the production of CCL17 by Langerhans cells and would explain the role of colonization by S aureus in patients with atopic dermatitis.
authors: Department of Immunobiology, Meiji Pharmaceutical University, Tokyo, Japan. kmatsui@my-pharm.ac.jp
authors: K
authors: K
authors: Matsui
authors: A
authors: A
authors: Nishikawa
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D054414:Chemokine CCL17 / Q000235:genetics / Q000378:metabolism; D054422:Chemokine CCL22 / Q000235:genetics / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D007114:Immunization; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010457:Peptidoglycan / Q000008:administration & dosage*; D039981:Pyroglyphidae; D054398:Receptors, CCR4 / Q000096:biosynthesis; D012867:Skin / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013211:Staphylococcus aureus / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D039741:Antigens, Dermatophagoides; C515355:Ccr4 protein, mouse; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D010457:Peptidoglycan; D054398:Receptors, CCR4