51. A novel role for type 1 angiotensin receptors on T lymphocytes to limit target organ damage in hypertension
- Author
-
Zhang, Jian-dong, Patel, Mehul B., Song, Young-Soo, Griffiths, Robert, Burchette, James, Ruiz, Phillip, Sparks, Matthew A., Yan, Ming, Howell, David N., Gomez, Jose A., Spurney, Robert F., Wilson, Christopher B., Coffman, Thomas M., and Crowley, Steven D.
- Subjects
CD4-Positive T-Lymphocytes ,Angiotensin receptor ,medicine.medical_specialty ,Mice, 129 Strain ,Physiology ,T cell ,Biology ,Kidney ,Article ,Receptor, Angiotensin, Type 1 ,TCIRG1 ,Interleukin 21 ,Mice ,Internal medicine ,medicine ,Cytotoxic T cell ,Animals ,IL-2 receptor ,Receptor ,Mice, Knockout ,Cell Differentiation ,Angiotensin II ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Endocrinology ,Hypertension ,Cardiology and Cardiovascular Medicine - Abstract
Rationale: Human clinical trials using type 1 angiotensin (AT 1 ) receptor antagonists indicate that angiotensin II is a critical mediator of cardiovascular and renal disease. However, recent studies have suggested that individual tissue pools of AT 1 receptors may have divergent effects on target organ damage in hypertension. Objective: We examined the role of AT 1 receptors on T lymphocytes in the pathogenesis of hypertension and its complications. Methods and Results: Deficiency of AT 1 receptors on T cells potentiated kidney injury during hypertension with exaggerated renal expression of chemokines and enhanced accumulation of T cells in the kidney. Kidneys and purified CD4 + T cells from “T cell knockout” mice lacking AT 1 receptors on T lymphocytes had augmented expression of Th1-associated cytokines including interferon-γ and tumor necrosis factor-α. Within T lymphocytes, the transcription factors T-bet and GATA-3 promote differentiation toward the Th1 and Th2 lineages, respectively, and AT 1 receptor-deficient CD4 + T cells had enhanced T-bet/GATA-3 expression ratios favoring induction of the Th1 response. Inversely, mice that were unable to mount a Th1 response due to T-bet deficiency were protected from kidney injury in our hypertension model. Conclusions: The current studies identify an unexpected role for AT 1 receptors on T lymphocytes to protect the kidney in the setting of hypertension by favorably modulating CD4 + T helper cell differentiation.
- Published
- 2012