Ultraviolet B Exposure Inhibits Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Mice by Expanding CD4+Foxp3+ Regulatory T Cells

J Am Heart Assoc. 2017 Aug 31;6(9):e007024. doi: 10.1161/JAHA.117.007024.

Abstract

Background: Pathogenic immune responses are known to play an important role in abdominal aortic aneurysm (AAA) development. Ultraviolet B (UVB) irradiation has been demonstrated to have therapeutic potential not only for cutaneous diseases but also for systemic inflammatory diseases in mice by suppressing immunoinflammatory responses. We investigated the effect of UVB irradiation on experimental AAA.

Methods and results: We used an angiotensin II-induced AAA model in apolipoprotein E-deficient mice fed a high-cholesterol diet. Mice aged 10 weeks were irradiated with 5 kJ/m2 UVB once weekly for 6 weeks (UVB-irradiated, n=38; nonirradiated, n=42) and were euthanized for evaluation of AAA formation at 16 weeks. Overall, 93% of angiotensin II-infused mice developed AAA, with 60% mortality possibly because of aneurysm rupture. UVB irradiation significantly decreased the incidence (66%) and mortality (29%) of AAA (P=0.004 and P=0.006, respectively). UVB-irradiated mice had significantly smaller diameter AAA (P=0.008) and fewer inflammatory cells in the aortic aneurysm tissue than nonirradiated mice, along with systemic expansion of CD4+Foxp3+ regulatory T cells and decreased effector CD4+CD44highCD62Llow T cells in para-aortic lymph nodes. Genetic depletion of regulatory T cells abrogated these beneficial effects of UVB treatment, demonstrating a critical role of regulatory T cells.

Conclusions: Our data suggest that UVB-dependent expansion of regulatory T cells has beneficial effects on experimental AAA and may provide a novel strategy for the treatment of AAA.

Keywords: abdominal aortic aneurysm; immunology; inflammation.

MeSH terms

  • Angiotensin II*
  • Animals
  • Aorta, Abdominal / immunology
  • Aorta, Abdominal / pathology
  • Aorta, Abdominal / radiation effects*
  • Aortic Aneurysm, Abdominal / chemically induced
  • Aortic Aneurysm, Abdominal / immunology
  • Aortic Aneurysm, Abdominal / pathology
  • Aortic Aneurysm, Abdominal / prevention & control*
  • Aortic Rupture / immunology
  • Aortic Rupture / pathology
  • Aortic Rupture / prevention & control
  • Cell Proliferation / radiation effects*
  • Cholesterol, Dietary
  • Disease Models, Animal
  • Forkhead Transcription Factors / immunology*
  • Lymph Nodes / immunology
  • Lymph Nodes / radiation effects*
  • Lymphocyte Activation / radiation effects*
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout, ApoE
  • Phenotype
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / radiation effects*
  • Time Factors
  • Ultraviolet Therapy*

Substances

  • Cholesterol, Dietary
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Angiotensin II