A novel role for type 1 angiotensin receptors on T lymphocytes to limit target organ damage in hypertension.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Zhang, J-D; Patel, MB; Song, Y-S; Griffiths, R; Burchette, J; Ruiz, P; Sparks, MA; Yan, M; Howell, DN; Gomez, JA; Spurney, RF; Coffman, TM; Crowley, SD

Published Date

  • June 8, 2012

Published In

Volume / Issue

  • 110 / 12

Start / End Page

  • 1604 - 1617

PubMed ID

  • 22534490

Pubmed Central ID

  • 22534490

Electronic International Standard Serial Number (EISSN)

  • 1524-4571

Digital Object Identifier (DOI)

  • 10.1161/CIRCRESAHA.111.261768

Language

  • eng

Conference Location

  • United States