Targeting CD44 augments the efficacy of Tregs in autoimmune diabetes.

Curing type 1 diabetes (T1D) will require lasting control of the autoimmune response that destroys insulin-producing islet β-cells. Re-establishing tolerance by restoring/replacing Tregs has significant potential for treatment of T1D but will require strategies to augment and maintain their efficacy. We previously showed that polyclonal in vitro-induced Tregs can reverse recent onset of T1D in ∼ 50% of NOD mice.

Islet antigen-specific Th17 cells can induce TNF-α-dependent autoimmune diabetes.

Type 1 diabetes (T1D) results from autoimmune destruction of pancreatic β-cells. Although Th1 cells are key orchestrators of T1D, the function(s) of the more recently identified Th17 subset are unclear due to inherent plasticity. In this study, we analyzed Th17 cells for stability and diabetogenicity in NOD mice.

Electrical remodelling precedes heart failure in an endothelin-1-induced model of cardiomyopathy.

Aims: Binary transgenic (BT) mice with doxycycline (DOX)-suppressible cardiac-specific overexpression of endothelin-1 (ET-1) exhibit progressive heart failure (HF), QRS prolongation, and death following DOX withdrawal. However, the molecular basis and reversibility of the electrophysiological abnormalities in this model were not known. Here, we assess the mechanisms underlying ET-1-mediated electrical remodelling, and its role in HF.

Protein kinase A-mediated phosphorylation contributes to enhanced contraction observed in mice that overexpress beta-adrenergic receptor kinase-1.

Transgenic mice with cardiac specific overexpression of beta-adrenergic receptor kinase-1 (betaARK-1) exhibit reduced contractility in the presence of adrenergic stimulation. However, whether contractility is altered in the absence of exogenous agonist is not clear. Effects of betaARK-1 overexpression on contraction were examined in mouse ventricular myocytes, studied at 37 degrees C, in the absence of adrenergic stimulation.