title: IL-17A is a novel player in dialysis-induced peritoneal damage.
abstract: The classical view of the immune system has changed by the discovery of novel T-helper (Th) subsets, including Th17 (IL-17A-producing cells). IL-17A participates in immune-mediated glomerulonephritis and more recently in inflammatory pathologies, including experimental renal injury. Peritoneal dialysis patients present chronic inflammation and Th1/Th2 imbalance, but the role of the Th17 response in peritoneal membrane damage has not been investigated. In peritoneal biopsies from dialyzed patients, IL-17A immunostaining was found mainly in inflammatory areas and was absent in the healthy peritoneum. IL-17A-expressing cells included lymphocytes (CD4+ and γδ), neutrophils, and mast cells. Elevated IL-17A effluent concentrations were found in long-term peritoneal dialysis patients. Studies in mice showed that repeated exposure to recombinant IL-17A caused peritoneal inflammation and fibrosis. Moreover, chronic exposure to dialysis fluids resulted in a peritoneal Th17 response, including elevated IL-17A gene and protein production, submesothelial cell infiltration of IL-17A-expressing cells, and upregulation of Th17 differentiation factors and cytokines. IL-17A neutralization diminished experimental peritoneal inflammation and fibrosis caused by chronic exposure to dialysis fluids in mice. Thus, IL-17A is a key player of peritoneum damage and it may be a good candidate for therapeutic intervention in peritoneal dialysis patients.
authors.affiliation: Cellular Biology in Renal Diseases Laboratory, IIS-Fundación Jiménez Díaz/Universidad Autónoma Madrid, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Rodrigues-Díez
authors.affiliation: Division of Nephrology, Hospital Universitario La Paz- IdiPAZ, Madrid, Spain.
authors.forename: Luiz S
authors.initials: LS
authors.lastname: Aroeira
authors.affiliation: Division of Nephrology, Hospital Universitario La Paz- IdiPAZ, Madrid, Spain.
authors.forename: Macarena
authors.initials: M
authors.lastname: Orejudo
authors.affiliation: Division of Nephrology, Hospital Universitario La Paz- IdiPAZ, Madrid, Spain.
authors.forename: M-Auxiliadora
authors.initials: MA
authors.lastname: Bajo
authors.affiliation: Servicio de Anatomia Patológica, Hospital de la Princesa, Madrid, Spain.
authors.forename: José Jiménez
authors.initials: JJ
authors.lastname: Heffernan
authors.affiliation: Cellular Biology in Renal Diseases Laboratory, IIS-Fundación Jiménez Díaz/Universidad Autónoma Madrid, Madrid, Spain.
authors.forename: Raúl R
authors.initials: RR
authors.lastname: Rodrigues-Díez
authors.affiliation: Cellular Biology in Renal Diseases Laboratory, IIS-Fundación Jiménez Díaz/Universidad Autónoma Madrid, Madrid, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rayego-Mateos
authors.affiliation: CIBERDEM (Biomedical Research Centre in Diabetes and Associated Metabolic Disorders), Division of Nephrology and Hypertension, IIS-Fundación Jiménez Díaz/Universidad Autónoma Madrid, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
authors.affiliation: Division of Nephrology, Hospital Universitario La Paz- IdiPAZ, Madrid, Spain.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Gonzalez-Mateo
authors.affiliation: Centro de Biología Molecular-Severo Ochoa, CSIC-UAM, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: López-Cabrera
authors.affiliation: Division of Nephrology, Hospital Universitario La Paz- IdiPAZ, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Selgas
authors.affiliation: CIBERDEM (Biomedical Research Centre in Diabetes and Associated Metabolic Disorders), Division of Nephrology and Hypertension, IIS-Fundación Jiménez Díaz/Universidad Autónoma Madrid, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
authors.affiliation: Cellular Biology in Renal Diseases Laboratory, IIS-Fundación Jiménez Díaz/Universidad Autónoma Madrid, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Ruiz-Ortega
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage; D016207:Cytokines / Q000378:metabolism; D015314:Dialysis Solutions / Q000009:adverse effects; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010537:Peritoneum / Q000276:immunology* / Q000293:injuries* / Q000473:pathology; D010538:Peritonitis / Q000209:etiology / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D016207:Cytokines; D015314:Dialysis Solutions; C508717:IL17A protein, human; D020381:Interleukin-17; D014157:Transcription Factors