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CCL22 acts on CCR4-expressing cells including Th2 and Treg. Although a correlation between the CCL22-CCR4 axis and allergic diseases has been established, the mechanism of monocyte lineage-specific <jats:italic>Ccl22<\/jats:italic> gene expression is largely unknown. In the current study, we investigated transcriptional regulation of the <jats:italic>Ccl22<\/jats:italic> gene in DCs and macrophages. Using reporter assays, we identified the critical <jats:italic>cis<\/jats:italic>-enhancing elements at 21\/\u221218 and \u221210\/\u22124 in the <jats:italic>Ccl22<\/jats:italic> promoter. Electrophoretic mobility shift assays proved that transcription factor PU.1 directly binds to the <jats:italic>cis<\/jats:italic>-elements. Knockdown of PU.1 markedly decreased <jats:italic>Ccl22<\/jats:italic> expression in bone marrow-derived DCs (BMDCs) and BM macrophages (BMDMs). Chromatin immunoprecipitation assays revealed that PU.1 bound to the <jats:italic>Ccl22<\/jats:italic> promoter in not only BMDCs and BMDMs, but also splenic DCs and peritoneal macrophages. LPS stimulation increased the amount of PU.1 recruited to the promoter, accompanied by upregulation of the <jats:italic>Ccl22<\/jats:italic> mRNA level, which was diminished by <jats:italic>Spi1<\/jats:italic> knockdown. We identified similar <jats:italic>cis<\/jats:italic>-elements on the human <jats:italic>CCL22<\/jats:italic> promoter, which were bound with PU.1 in human monocytes. Taken together, these findings indicate that PU.1 transactivates the <jats:italic>Ccl22<\/jats:italic> gene in DCs and macrophages by directly binding to the two elements in the promoter.<\/jats:p>","DOI":"10.1038\/s41598-018-37894-9","type":"journal-article","created":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T11:04:09Z","timestamp":1549278249000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["A transcription factor PU.1 is critical for Ccl22 gene expression in dendritic cells and macrophages"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9319-3467","authenticated-orcid":false,"given":"Takuya","family":"Yashiro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiori","family":"Nakano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurumi","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuna","family":"Uchida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumi","family":"Kasakura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4082-9097","authenticated-orcid":false,"given":"Chiharu","family":"Nishiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,2,4]]},"reference":[{"key":"37894_CR1","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1189\/jlb.69.5.785","volume":"69","author":"JL Vissers","year":"2001","unstructured":"Vissers, J. 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