Cytotoxic T Lymphocyte-Associated Antigen-4 Protects Against Angiotensin II-Induced Kidney Injury in Mice

Background: Chronic inflammation caused by pathogenic immune response is crucial in the pathogenesis of kidney disease. In particular, T-cell-mediated adaptive immune responses evoke pathogenic immunoinflammatory responses and contribute to kidney injury (KI). Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), a potent negative regulator of T-cell immune responses, protects against immunoinflammatory diseases of the arteries such as atherosclerosis and abdominal aortic aneurysm. However, the role of this molecule in kidney disease remains undetermined. Methods and Results: To examine the effects of CTLA-4 overexpression on angiotensin II (AngII)-induced KI, we induced KI in CTLA-4 transgenic/apolipoprotein E-deficient (CTLA-4-Tg/Apoe(−/−)) mice or Apoe(−/−) mice fed a high-cholesterol diet by continuously infusing AngII. Overexpression of CTLA-4 ameliorated the development of AngII-induced KI and fibrosis. Moreover, CTLA-4-Tg/Apoe(−/−) mice had decreased expression of pro-inflammatory molecules in the kidney. Conclusions: CTLA-4 overexpression has a protective effect on AngII-induced KI, and increasing CTLA-4 may be a novel therapeutic strategy to prevent the progression of kidney disease.