title: Regulatory T cells in human and angiotensin II-induced mouse abdominal aortic aneurysms.
abstract: OBJECTIVE
  Regulatory T cells (Tregs) protect mice from angiotensin II (Ang-II)-induced abdominal aortic aneurysms (AAA). This study tested whether AAA patients are Treg-insufficient and the Treg molecular mechanisms that control AAA pathogenesis.
  
  
  RESULTS
  ELISA determined the Foxp3 concentration in blood cell lysates from 485 AAA patients and 204 age- and sex-matched controls. AAA patients exhibited lower blood cell Foxp3 expression than controls (P < 0.0001). Pearson's correlation test demonstrated a significant but negative correlation between Foxp3 and AAA annual expansion rate before (r = -0.147, P = 0.007) and after (r = -0.153, P = 0.006) adjustment for AAA risk factors. AAA in apolipoprotein E-deficient (Apoe(-/-)) mice that received different doses of Ang-II exhibited a negative correlation of lesion Foxp3(+) Treg numbers with AAA size (r = -0.883, P < 0.0001). Adoptive transfer of Tregs from wild-type (WT) and IL10-deficient (Il10(-/-)) mice increased AAA lesion Treg content, but only WT mice Tregs reduced AAA size, AAA incidence, blood pressure, lesion macrophage and CD4(+) and CD8(+) T-cell accumulation, and angiogenesis with concurrent increase of lesion collagen content. Both AAA lesion immunostaining and plasma ELISA demonstrated that adoptive transfer of WT Tregs, but not Il10(-/-) Tregs, reduced the expression of MCP-1. In vitro cell culture and aortic ring assay demonstrated that only Tregs from WT mice, but not those from Il10(-/-) mice, reduced macrophage MCP-1 secretion, macrophage and vascular cell protease expression and activity, and aortic ring microvessel formation.
  
  
  CONCLUSIONS
  This study supports a protective role of Tregs in human and experimental AAA by releasing IL10 to suppress inflammatory cell chemotaxis, arterial wall remodelling, and angiogenesis.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB-7, Boston, MA 02115, USA Department of Nephrology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB-7, Boston, MA 02115, USA College of Veterinary Medicine, China Agriculture University, Beijing 100193, China.
authors.forename: Wenxue
authors.initials: W
authors.lastname: Wu
authors.affiliation: Elitary Research Centre of Individualized Medicine in Arterial Diseases, Department of Cardiothoracic and Vascular Surgery, University Hospital of Odense, Odense DK-5000, Denmark.
authors.forename: Jes S
authors.initials: JS
authors.lastname: Lindholt
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB-7, Boston, MA 02115, USA.
authors.forename: Galina K
authors.initials: GK
authors.lastname: Sukhova
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB-7, Boston, MA 02115, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
authors.affiliation: Department of Nephrology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China gshi@rics.bwh.harvard.edu yuxq@mail.sysu.edu.cn.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB-7, Boston, MA 02115, USA gshi@rics.bwh.harvard.edu yuxq@mail.sysu.edu.cn.
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Shi
mesh_terms: D000368:Aged; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000209:etiology / Q000517:prevention & control*; D018925:Chemokines / Q000096:biosynthesis; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
chemical_list: D018925:Chemokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D000804:Angiotensin II; D016753:Interleukin-10
keywords: Abdominal aortic aneurysm; Adoptive transfer; Inflammatory cell; Interleukin-10; Regulatory T-cell
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