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However, it is unknown whether it contributes to acute kidney injury (AKI). We identified CCL20 as upregulated in a systems biology strategy combining transcriptomics of kidney tissue from experimental toxic folic acid\u2010induced AKI and from stressed cultured tubular cells and have explored the expression and function of CCL20 in experimental and clinical AKI. CCL20 upregulation was confirmed in three models of kidney injury induced by a folic acid overdose, cisplatin or unilateral ureteral obstruction. In injured kidneys, CCL20 was expressed by tubular, endothelial, and interstitial cells, and was also upregulated in human kidneys with AKI. Urinary CCL20 was increased in human AKI and was associated with severity. The function of CCL20 in nephrotoxic folic acid\u2010induced AKI was assessed by using neutralising anti\u2010CCL20 antibodies or CCR6\u2010deficient mice. CCL20\/CCR6 targeting increased the severity of kidney failure and mortality. This was associated with more severe histological injury, nephrocalcinosis, capillary rarefaction, and fibrosis, as well as higher expression of tubular injury\u2010associated genes. Surprisingly, mice with CCL20 blockade had a lower tubular proliferative response and a higher number of cells in the G2\/M phase, suggesting impaired repair mechanisms. This may be related to a lower influx of Tregs, despite a milder inflammatory response in terms of chemokine expression and infiltration by IL\u201017\n                    <jats:sup>+<\/jats:sup>\n                    cells and neutrophils. In conclusion, CCL20 has a nephroprotective role during AKI, both by decreasing tissue injury and by facilitating repair. Copyright \u00a9 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.5132","type":"journal-article","created":{"date-parts":[[2018,7,9]],"date-time":"2018-07-09T02:40:41Z","timestamp":1531104041000},"page":"191-204","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["CCL20 blockade increases the severity of nephrotoxic folic acid\u2010induced acute kidney injury"],"prefix":"10.1002","volume":"246","author":[{"given":"Cristian","family":"Gonz\u00e1lez\u2010Guerrero","sequence":"first","affiliation":[{"name":"Laboratory of Nephrology, IIS\u2010Fundaci\u00f3n Jim\u00e9nez D\u00edaz School of Medicine  UAM, Madrid Spain"},{"name":"Red de Investigaci\u00f3n Renal (REDINREN)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Luis","family":"Morgado\u2010Pascual","sequence":"additional","affiliation":[{"name":"Laboratory of Nephrology, IIS\u2010Fundaci\u00f3n Jim\u00e9nez D\u00edaz School of Medicine  UAM, Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Cannata\u2010Ortiz","sequence":"additional","affiliation":[{"name":"Pathology IIS\u2010Fundaci\u00f3n Jim\u00e9nez D\u00edaz, School of Medicine  UAM, Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Angeles","family":"Ramos\u2010Barron","sequence":"additional","affiliation":[{"name":"Nephrology Investigation Unit University Hospital Marqu\u00e9s de Valdecilla  IDIVAL (Instituto de Investigacion Valdecilla), Santander Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"G\u00f3mez\u2010Alamillo","sequence":"additional","affiliation":[{"name":"Red de Investigaci\u00f3n Renal (REDINREN)"},{"name":"Nephrology Investigation Unit University Hospital Marqu\u00e9s de Valdecilla  IDIVAL (Instituto de Investigacion Valdecilla), Santander Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Arias","sequence":"additional","affiliation":[{"name":"Red de Investigaci\u00f3n Renal (REDINREN)"},{"name":"Nephrology Investigation Unit University Hospital Marqu\u00e9s de Valdecilla  IDIVAL (Instituto de Investigacion Valdecilla), Santander Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Mezzano","sequence":"additional","affiliation":[{"name":"Division of Nephrology, School of Medicine Universidad Austral de Chile  Valdivia Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Egido","sequence":"additional","affiliation":[{"name":"IIS\u2010Fundaci\u00f3n Jim\u00e9nez D\u00edaz School of Medicine  UAM, Madrid Spain"},{"name":"Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM)  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Ruiz\u2010Ortega","sequence":"additional","affiliation":[{"name":"Red de Investigaci\u00f3n Renal (REDINREN)"},{"name":"Cellular Biology in Renal Diseases Laboratory. 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