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Considering a proangiogenic effect of CCL20 on endothelial cells via CCR6, the CCL20\/CCR6 axis may contribute to the development of SSc vasculopathy. Therefore, we explored this hypothesis using clinical samples, cultured cells, and murine SSc models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The expression levels of CCL20 and CCR6 in the skin, mRNA levels of target genes, and the binding of transcription factor FLI1 to the target gene promoter were evaluated by immunostaining, quantitative reverse transcription PCR, and chromatin immunoprecipitation, respectively. Vascular permeability was evaluated by Evans blue dye injection in bleomycin-treated mice. Angiogenic activity of endothelial cells was assessed by in vitro angiogenesis assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CCL20 expression was significantly elevated in dermal fibroblasts of patients with early diffuse cutaneous SSc, while CCR6 was significantly up-regulated in dermal small vessels of SSc patients irrespective of disease subtypes and disease duration. In human dermal microvascular endothelial cells,\n                      <jats:italic>FLI1<\/jats:italic>\n                      siRNA induced the expression of CCR6, but not CCL20, and FLI1 bound to the\n                      <jats:italic>CCR6<\/jats:italic>\n                      promoter. Importantly, vascular permeability, a representative SSc-like vascular feature of bleomycin-treated mice, was attenuated by\n                      <jats:italic>Ccr6<\/jats:italic>\n                      siRNA treatment, and\n                      <jats:italic>CCR6<\/jats:italic>\n                      siRNA suppressed the angiogenic activity of human dermal microvascular endothelial cells assayed by in vitro tube formation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The increased expression of endothelial CCR6 due to FLI1 deficiency may contribute to the development of SSc vasculopathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13075-021-02667-9","type":"journal-article","created":{"date-parts":[[2021,11,13]],"date-time":"2021-11-13T02:02:36Z","timestamp":1636768956000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Endothelial CCR6 expression due to FLI1 deficiency contributes to vasculopathy associated with systemic sclerosis"],"prefix":"10.1186","volume":"23","author":[{"given":"Tetsuya","family":"Ikawa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuya","family":"Miyagawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Fukui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Toyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Omatsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kentaro","family":"Awaji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuta","family":"Norimatsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayumi","family":"Yoshizaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichi","family":"Sato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5560-9778","authenticated-orcid":false,"given":"Yoshihide","family":"Asano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,11,13]]},"reference":[{"issue":"2","key":"2667_CR1","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1111\/1346-8138.14153","volume":"45","author":"Y Asano","year":"2018","unstructured":"Asano Y. 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