title: TLR2 down-regulates FcεRI and its transcription factor PU.1 in human Langerhans cells.
abstract: BACKGROUND
  Epidermal Langerhans cells (LC) expressing the high-affinity receptor for IgE (FcεRI) play a key role in atopic dermatitis (AD). AD skin is highly colonized with Staphylococcus aureus (S.a.), which are sensed by Toll-like receptor 2 (TLR2). We hypothesized that TLR2 may impact on the expression of FcεRI on LC.
  
  
  OBJECTIVE
  To study a putative impact of TLR2 signaling on FcεRI, we analyzed FcεRI and known transcription factors of the receptor after ligand binding to TLR2.
  
  
  METHODS
  We generated LC from CD34(+) progenitors in vitro (CD34LC) expressing FcεRI and TLR2 as well as its partners TLR1 and TLR6. The expression of FcεRI and known transcription factors of the receptor was analyzed on the protein and RNA level by flow cytometry, Western blotting, and real-time PCR.
  
  
  RESULTS
  For CD34LC from 123 donors, we observed a high heterogeneity in FcεRI surface expression correlating with mRNA level of its α-chain. Stimulation of TLR1/2 or TLR2/6 dramatically down-regulated FcεRI on protein and mRNA level of both α- and γ-chain. Further analysis of putative transcription factors for FCER1A revealed the lack of GATA1 in CD34LC, weak expression of ELF1 and YY1, and high expression of PU.1. While ELF1 and YY1 appeared to be little affected by TLR2 engagement, PU.1 was significantly down-regulated.
  
  
  CONCLUSIONS
  Taken together, our findings show that in human, LC ligation of TLR2 by S.a.-derived products down-regulates FcεRI and its transcription factor PU.1, thus suggesting that FcεRI is controlled by PU.1 in these cells.
authors.affiliation: Department of Dermatology and Allergy, University of Bonn, D-53105 Bonn, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Herrmann
authors.forename: S
authors.initials: S
authors.lastname: Koch
authors.forename: N
authors.initials: N
authors.lastname: Leib
authors.forename: J
authors.initials: J
authors.lastname: Bedorf
authors.forename: H
authors.initials: H
authors.lastname: Wilms
authors.forename: S
authors.initials: S
authors.lastname: Schnautz
authors.forename: R
authors.initials: R
authors.lastname: Fimmers
authors.forename: T
authors.initials: T
authors.lastname: Bieber
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D002478:Cells, Cultured; D015870:Gene Expression; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D007801:Langerhans Cells / Q000378:metabolism*; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D017455:Receptors, IgE / Q000235:genetics* / Q000378:metabolism; D051194:Toll-Like Receptor 1 / Q000235:genetics / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051216:Toll-Like Receptor 6 / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D018952:Antigens, CD34; D011518:Proto-Oncogene Proteins; D017455:Receptors, IgE; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1