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PMID: 16810739 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

IL-4 induces expression of TARC/CCL17 via two STAT6 binding sites.

European journal of immunology ·Vol. 36 ·No. 7 ·2006-07-00 ·Pages 1882-91

Wirnsberger G, Hebenstreit D, Posselt G, Horejs-Hoeck J, Duschl A

Abstract

A cardinal feature of allergic disorders and immune responses is enhanced leukocyte trafficking. This is largely orchestrated by chemokines. The CC chemokine thymus- and activation-regulated chemokine (TARC/CCL17) selectively attracts Th2 cells via the G protein-coupled chemokine receptor CCR4. We show here that TARC/CCL17 is expressed by human T cells upon stimulation with IL-4. Mapping of the transcriptional start site revealed the presence of two putative STAT6 binding motifs in proximity to the start position. EMSA and chromatin immunoprecipitation experiments demonstrated that STAT6 was able to bind to both motifs. A fragment of the TARC/CCL17 promoter containing both sites was tested in reporter gene assays for IL-4 inducibility. The promoter was inducible in a STAT6-deficient cell line only after introduction of functional STAT6. When mutations were inserted into one of the STAT6 motifs, IL-4-induced promoter activation was reduced. With both sites mutated, inducibility was completely abrogated. These data demonstrate collectively that T cells serve as a source of TARC/CCL17 when stimulated with IL-4 and that STAT6 is essential for this.

MeSH Terms
Adult Binding Sites Cells, Cultured Chemokine CCL17 Chemokines, CC/biosynthesis,genetics Gene Expression Regulation/physiology Humans Interleukin-4/physiology Promoter Regions, Genetic STAT6 Transcription Factor/genetics,metabolism T-Lymphocytes/metabolism
Chemicals
CCL17 protein, human Chemokine CCL17 Chemokines, CC IL4 protein, human STAT6 Transcription Factor STAT6 protein, human Interleukin-4
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Wirnsberger Gerald
Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
Hebenstreit Daniel
Posselt Gernot
Horejs-Hoeck Jutta
Duschl Albert
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Article Info
Journal
European journal of immunology
Abbr.
Eur J Immunol
ISSN
0014-2980
DOI
10.1002/eji.200635972
Published
2006-07-00
Pages
1882-91
Language
English
Region
Germany
NLM ID
1273201
PMCID
PMC2988193
Subset
IM
Grants
Austrian Science Fund FWF · P 18409 · Austria
External Links
PubMed source DOI: 10.1002/eji.200635972 PMC Full Text View journal details
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