title: A novel role for type 1 angiotensin receptors on T lymphocytes to limit target organ damage in hypertension.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Division of Nephrology, Departments of Medicine, Duke University Medical Center and Durham VA Medical Center, Durham, NC 27710, USA.
authors.forename: Jian-dong
authors.initials: JD
authors.lastname: Zhang
authors.forename: Mehul B
authors.initials: MB
authors.lastname: Patel
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Song
authors.forename: Robert
authors.initials: R
authors.lastname: Griffiths
authors.forename: James
authors.initials: J
authors.lastname: Burchette
authors.forename: Phillip
authors.initials: P
authors.lastname: Ruiz
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Sparks
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.forename: David N
authors.initials: DN
authors.lastname: Howell
authors.forename: Jose A
authors.initials: JA
authors.lastname: Gomez
authors.forename: Robert F
authors.initials: RF
authors.lastname: Spurney
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Coffman
authors.forename: Steven D
authors.initials: SD
authors.lastname: Crowley
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D007668:Kidney / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*
chemical_list: D044140:Receptor, Angiotensin, Type 1