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.Fil: Fabbiano, Salvatore. Consejo Superior de Investigaciones Científicas; España. Universidad de Salamanca; España. Instituto de Biología Molecular y Celular del Cáncer de Salamanca; España; EspañaFil: Menacho Márquez, Mauricio Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Superior de Investigaciones Científicas; España. Universidad de Salamanca; EspañaFil: Robles Valero, Javier. Consejo Superior de Investigaciones Científicas; España. Universidad de Salamanca; EspañaFil: Pericacho, Miguel. Universidad de Salamanca; EspañaFil: Matesanz Marín, Adela. Centro Nacional de Investigaciones Cardiovasculares; EspañaFil: García Macías, Carmen. Consejo Superior de Investigaciones Científicas; España. Universidad de Salamanca; EspañaFil: Sevilla, María A.. Universidad de Salamanca; EspañaFil: Montero, M. J.. Universidad de Salamanca; EspañaFil: Alarcón, Balbino. Consejo Superior de Investigaciones Científicas; EspañaFil: López Novoa, José M.. Universidad de Salamanca; EspañaFil: Martín, Pilar. Consejo Superior de Investigaciones Científicas; EspañaFil: Bustelo, Xosé R.. Consejo Superior de Investigaciones Científicas; España. Universidad de Salamanca; Españ