title: Immunosuppression-Independent Role of Regulatory T Cells against Hypertension-Driven Renal Dysfunctions.
abstract: Hypertension-associated cardiorenal diseases represent one of the heaviest burdens for current health systems. In addition to hemodynamic damage, recent results have revealed that hematopoietic cells contribute to the development of these diseases by generating proinflammatory and profibrotic environments in the heart and kidney. However, the cell subtypes involved remain poorly characterized. Here we report that CD39(+) regulatory T (TREG) cells utilize an immunosuppression-independent mechanism to counteract renal and possibly cardiac damage during angiotensin II (AngII)-dependent hypertension. This mechanism relies on the direct apoptosis of tissue-resident neutrophils by the ecto-ATP diphosphohydrolase activity of CD39. In agreement with this, experimental and genetic alterations in TREG/TH cell ratios have a direct impact on tissue-resident neutrophil numbers, cardiomyocyte hypertrophy, cardiorenal fibrosis, and, to a lesser extent, arterial pressure elevation during AngII-driven hypertension. These results indicate that TREG cells constitute a first protective barrier against hypertension-driven tissue fibrosis and, in addition, suggest new therapeutic avenues to prevent hypertension-linked cardiorenal diseases.
authors.affiliation: Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-University of Salamanca, Salamanca, Spain Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-University of Salamanca, Salamanca, Spain.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Fabbiano
authors.affiliation: Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-University of Salamanca, Salamanca, Spain Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-University of Salamanca, Salamanca, Spain.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Menacho-Márquez
authors.affiliation: Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-University of Salamanca, Salamanca, Spain Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-University of Salamanca, Salamanca, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Robles-Valero
authors.affiliation: Departamento de Fisiología y Farmacología, University of Salamanca, Salamanca, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Pericacho
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Adela
authors.initials: A
authors.lastname: Matesanz-Marín
authors.affiliation: Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-University of Salamanca, Salamanca, Spain Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-University of Salamanca, Salamanca, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: García-Macías
authors.affiliation: Departamento de Fisiología y Farmacología, University of Salamanca, Salamanca, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Sevilla
authors.affiliation: Departamento de Fisiología y Farmacología, University of Salamanca, Salamanca, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Montero
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC, Madrid, Spain.
authors.forename: Balbino
authors.initials: B
authors.lastname: Alarcón
authors.affiliation: Departamento de Fisiología y Farmacología, University of Salamanca, Salamanca, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: López-Novoa
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Martín
authors.affiliation: Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-University of Salamanca, Salamanca, Spain Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-University of Salamanca, Salamanca, Spain xbustelo@usal.es.
authors.forename: Xosé R
authors.identifier: http://orcid.org/0000-0001-9398-6072
authors.initials: XR
authors.lastname: Bustelo
mesh_terms: D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D001081:Apyrase / Q000378:metabolism; D002478:Cells, Cultured; D005355:Fibrosis; D006973:Hypertension / Q000150:complications* / Q000276:immunology; D007108:Immune Tolerance; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D009504:Neutrophils / Q000502:physiology; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics / Q000378:metabolism; D051437:Renal Insufficiency / Q000209:etiology / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D051567:Proto-Oncogene Proteins c-vav; C496619:Vav1 protein, mouse; D000804:Angiotensin II; D001081:Apyrase; C067869:CD39 antigen