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TLR 2 down‐regulates Fcε RI and its transcription factor PU .1 in human Langerhans cells
Author(s) -
Herrmann N.,
Koch S.,
Leib N.,
Bedorf J.,
Wilms H.,
Schnautz S.,
Fimmers R.,
Bieber T.
Publication year - 2013
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12145
Subject(s) - receptor , tlr2 , flow cytometry , transcription factor , messenger rna , microbiology and biotechnology , toll like receptor , biology , reverse transcription polymerase chain reaction , transcription (linguistics) , chemistry , tlr4 , innate immune system , gene , biochemistry , linguistics , philosophy
Background Epidermal Langerhans cells ( LC ) expressing the high‐affinity receptor for IgE (Fcε RI ) 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 ( TLR 2). We hypothesized that TLR 2 may impact on the expression of Fcε RI on LC . Objectives To study a putative impact of TLR 2 signaling on Fcε RI , we analyzed Fcε RI and known transcription factors of the receptor after ligand binding to TLR 2. Methods We generated LC from CD 34 + progenitors in vitro ( CD 34 LC ) expressing Fcε RI and TLR 2 as well as its partners TLR 1 and TLR 6. The expression of Fcε RI 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 TLR 1/2 or TLR 2/6 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 GATA 1 in CD34LC , weak expression of ELF 1 and YY 1, and high expression of PU .1. While ELF 1 and YY 1 appeared to be little affected by TLR 2 engagement, PU .1 was significantly down‐regulated. Conclusions Taken together, our findings show that in human, LC ligation of TLR 2 by S.a.‐derived products down‐regulates Fcε RI and its transcription factor PU .1, thus suggesting that Fcε RI is controlled by PU .1 in these cells.