CD4⁺CD25⁺Foxp3⁺ regulatory T cells suppress cardiac fibrosis in the hypertensive heart

Abstract

Background 

CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Tregs) are potent inhibitors of inflammation and autoimmune diseases. Because inflammation has been associated with development of cardiac fibrosis in experimental hypertension, here we investigated whether adoptively transferred Tregs would inhibit development of cardiac fibrosis initiated by elevating blood pressure.

Methods 

Cardiac fibrosis was induced in mice by constricting the aorta between the two carotid arteries. Immediately after the operation mice received either vehicle or purified, cultured Tregs (1.5 × 10⁶). Fourteen days later we assessed effects on developing left ventricular fibrosis, blood pressure, inflammation, myofibroblasts and the transforming growth factor-beta1 (TGF-β1) system.

Results 

Fourteen days after aortic constriction, marked left-ventricular fibrosis was apparent and this was greatly reduced in mice receiving adoptively transferred Tregs. This reduction in fibrosis was associated with attenuated inflammatory cell numbers, reduced interstitial myofibroblast numbers and attenuated activity of the TGF-β1 system, indicated by reductions in the expression of TGF-β1 and its receptors activin-like kinase-5 and type II TGF-β receptor. Adoptively transferred Tregs did not affect blood pressure and exerted only a small effect on left-ventricular hypertrophy.

Conclusions 

These data indicate that Tregs attenuate cardiac fibrosis associated with hypertensive heart disease by suppressing inflammation.