title: Deficiency of T-regulatory cells exaggerates angiotensin II-induced microvascular injury by enhancing immune responses.
abstract: OBJECTIVE
  T-regulatory lymphocyte (Treg) adoptive transfer prevented angiotensin (Ang) II-induced hypertension and microvascular injury. Scurfy mice are deficient in Treg because of a mutation in the transcription factor forkhead box P3 (Foxp3) gene. Enhanced Ang II effects in the absence of Treg would unambiguously demonstrate their vascular protective role. We hypothesized that adoptive transfer of Scurfy vs. wild-type T cells will exacerbate Ang II-induced microvascular damage in T and B-cell-deficient recombination-activating gene 1 (Rag1) knockout mice.
  
  
  RESULTS
  Rag1 knockout mice were injected with vehicle, 10(7) T cells from wild-type or Scurfy mice or 10 (6)wild-type Treg alone or in combination with Scurfy T cells, and then infused or not with Ang II (490 ng/kg per min, subcutaneous) for 14 days. Ang II increased SBP in all the groups, but DBP only in wild-type and Scurfy T-cell groups. Ang II-induced endothelial dysfunction and oxidative stress in perivascular adipose tissue (PVAT) of mesenteric arteries of the wild-type T-cell group, whereas these were exaggerated in the Scurfy T-cell group. Ang II enhanced microvascular remodeling and stiffness in vehicle and Scurfy T-cell groups. Ang II increased monocyte chemotactic protein-1 expression in the vascular wall and PVAT, monocyte/macrophage infiltration and proinflammatory polarization in PVAT and the renal cortex, and T-cell infiltration in the renal cortex only in the Scurfy T-cell group. Treg coinjection in the vehicle and Scurfy T-cell groups prevented or reduced the effects of Ang II.
  
  
  CONCLUSIONS
  FOXP3+ Treg deficiency exaggerates Ang II-induced microvascular injury by modulating innate and adaptive immune responses.
authors.affiliation: aLady Davis Institute for Medical Research bDepartment of Medicine, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Quebec, Canada cINSERM U1083, CNRS UMR 6214, Centre Hospitalo-Universitaire d'Angers, Université d'Angers, Angers, France.
authors.forename: Muhammad Oneeb Rehman
authors.initials: MO
authors.lastname: Mian
authors.forename: Tlili
authors.initials: T
authors.lastname: Barhoumi
authors.forename: Marie
authors.initials: M
authors.lastname: Briet
authors.forename: Pierre
authors.initials: P
authors.lastname: Paradis
authors.forename: Ernesto L
authors.initials: EL
authors.lastname: Schiffrin
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D019264:Adoptive Transfer; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D018791:CD4 Lymphocyte Count; D018932:Chemokine CCL2 / Q000378:metabolism; D004727:Endothelium / Q000187:drug effects / Q000503:physiopathology; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000172:deficiency / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006973:Hypertension / Q000378:metabolism; D007113:Immunity, Innate; D007672:Kidney Cortex / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D055806:Microvessels / Q000473:pathology*; D009000:Monocytes / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*; D066253:Vascular Remodeling / Q000187:drug effects; D059289:Vascular Stiffness / Q000187:drug effects
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018398:Homeodomain Proteins; D000804:Angiotensin II; C064658:RAG-1 protein