TLR2 down‐regulates FcεRI and its transcription factor PU.1 in human Langerhans cells. Issue 5 (27th March 2013)

• Record Type: Journal Article
• Authors: Herrmann, N.; Koch, S.; Leib, N.; Bedorf, J.; Wilms, H.; Schnautz, S.; Fimmers, R.; Bieber, T.
• Is Part Of: Allergy. Volume 68:Issue 5(2013:May)
• Page Start: 621
• Page End: 628
• Publication Date: 2013-03-27
• Subjects: Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.12145
• Languages: English
• ISSNs: 0105-4538

Abstract

<abstract abstract-type="main" xml:lang="en" id="all12145-abs-0001"> <title>Abstract</title> <sec id="all12145-sec-0001" sec-type="section"> <title>Background</title> <p>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 <italic>Staphylococcus aureus</italic> (S.a.), which are sensed by Toll‐like receptor 2 (TLR2). We hypothesized that TLR2 may impact on the expression of FcεRI on LC.</p> </sec> <sec id="all12145-sec-0002" sec-type="section"> <title>Objectives</title> <p>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.</p> </sec> <sec id="all12145-sec-0003" sec-type="section"> <title>Methods</title> <p>We generated LC from CD34<sup>+</sup> progenitors <italic>in vitro</italic> (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.</p> </sec> <sec id="all12145-sec-0004" sec-type="section"> <title>Results</title> <p>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.</p> </sec> <sec id="all12145-sec-0005" sec-type="section"> <title>Conclusions</title> <p>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.</p> </sec> </abstract>