title: Paricalcitol reduces peritoneal fibrosis in mice through the activation of regulatory T cells and reduction in IL-17 production.
abstract: Fibrosis is a significant health problem associated with a chronic inflammatory reaction. The precise mechanisms involved in the fibrotic process are still poorly understood. However, given that inflammation is a major causative factor, immunomodulation is a possible therapeutic approach to reduce fibrosis. The vitamin D receptor (VDR) that is present in all hematopoietic cells has been associated with immunomodulation. We investigated whether the intraperitoneal administration of paricalcitol, a specific activator of the VDR, modulates peritoneal dialysis fluid (PDF)-induced peritoneal fibrosis. We characterized the inflammatory process in the peritoneal cavity of mice treated or not treated with paricalcitol and analyzed the ensuing fibrosis. The treatment reduced peritoneal IL-17 levels, which strongly correlated with a significantly lower peritoneal fibrotic response. In vitro studies demonstrate that both CD4+ and CD8+ regulatory T cells appear to impact the regulation of IL-17. Paricalcitol treatment resulted in a significantly increased frequency of CD8+ T cells showing a regulatory phenotype. The frequency of CD4+ Tregs tends to be increased, but it did not achieve statistical significance. However, paricalcitol treatment increased the number of CD4+ and CD8+ Treg cells in vivo. In conclusion, the activation of immunological regulatory mechanisms by VDR signaling could prevent or reduce fibrosis, as shown in peritoneal fibrosis induced by PDF exposure in mice.
authors.affiliation: Research Department, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), Hospital La Paz, Madrid, Spain; Molecular Biology Center Severo Ochoa, CSIC-UAM, Madrid, Spain.
authors.forename: Guadalupe T
authors.initials: GT
authors.lastname: González-Mateo
authors.affiliation: Research Department, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), Hospital La Paz, Madrid, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Fernández-Míllara
authors.affiliation: Research Department, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), Hospital La Paz, Madrid, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Bellón
authors.affiliation: Molecular Biology Center Severo Ochoa, CSIC-UAM, Madrid, Spain.
authors.forename: Georgios
authors.initials: G
authors.lastname: Liappas
authors.affiliation: Cellular Biology in Renal Diseases Laboratory, IIS-Fundación Jiménez Díaz/Autonomous University of Madrid, Madrid, Spain; Red de Investigación Renal REDinREN, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Ruiz-Ortega
authors.affiliation: Molecular Biology Center Severo Ochoa, CSIC-UAM, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: López-Cabrera
authors.affiliation: Research Department, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), Hospital La Paz, Madrid, Spain; Nephrology Department, Hospital Universitario La Paz, Madrid, Spain; Red de Investigación Renal REDinREN, Madrid, Spain; Instituto Reina Sofía de Investigación en Nefrología (IRSIN), Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Selgas
authors.affiliation: Immunology Department, Centro de Investigaciones Biomédicas (CINBIO), Instituto de Investigación Biomédica de Vigo (IBIV), University of Vigo, Vigo, Spain.
authors.forename: Luiz S
authors.initials: LS
authors.lastname: Aroeira
mesh_terms: D000818:Animals; D018925:Chemokines / Q000096:biosynthesis; D004872:Ergocalciferols / Q000494:pharmacology*; D005260:Female; D020381:Interleukin-17 / Q000096:biosynthesis*; D018655:Lymphocyte Count; D051379:Mice; D056627:Peritoneal Fibrosis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*
chemical_list: D018925:Chemokines; D004872:Ergocalciferols; D020381:Interleukin-17; C084656:paricalcitol