MMUNOSUPPRESSION-INDEPENDENT ROLE OF REGULATORY T CELLS AGAINST HYPERTENSION-DRIVEN RENAL DYSFUNCTIONS

FABBIANO, S; MAURICIO ARIEL MENACHO; JAVIER ROBLES VALER; MIGUEL PERICACHO; MATESANZ, M; CARMEN GARCÍA-MATAS; SEVILLA, MA; MONTERO, MJ; BALBINO ALARCÓN; LOPEZ-NOVOA JM; MARTÍN, P; XOSÉ R. BUSTELO

MOLECULAR AND CELLULAR BIOLOGY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2015

0270-7306

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 heart and kidney. However, the cell subtypes involved remain poorly characterized. Here, we report that CD39+ 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-adenosine triphosphate diphosphohydrolase activity of CD39. Consistent 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, in 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.