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IL-4 induces expression of TARC/CCL17 via two STAT6 binding sites
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Wirnsberger, Gerald, Hebenstreit, Daniel, Posselt, Gernot, Horejs-Hoeck, Jutta and Duschl, Albert (2006) IL-4 induces expression of TARC/CCL17 via two STAT6 binding sites. European Journal of Immunology, Volume 36 (Number 7). pp. 1882-1891. doi:10.1002/eji.200635972 ISSN 0014-2980.
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Official URL: http://dx.doi.org/10.1002/eji.200635972
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.
Item Type: | Journal Article | ||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||
Journal or Publication Title: | European Journal of Immunology | ||||
Publisher: | Wiley - V C H Verlag GmbH & Co. KGaA | ||||
ISSN: | 0014-2980 | ||||
Official Date: | July 2006 | ||||
Dates: |
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Volume: | Volume 36 | ||||
Number: | Number 7 | ||||
Page Range: | pp. 1882-1891 | ||||
DOI: | 10.1002/eji.200635972 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access |
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