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

Hayashi, Tomohiro  ,  Sasaki, Naoto  ,  Yamashita, Tomoya  ,  Mizoguchi, Taiji  ,  Emoto, Takuo  ,  Amin, Hilman Zulkifli  ,  Yodoi, Keiko  ,  Matsumoto, Takuya  ,  Kasahara, Kazuyuki  ,  Yoshida, Naofumi  ,  Tabata, Tokiko  ,  Kitano, Naoki  ,  Fukunaga, Atsushi  ,  Nishigori, Chikako  ,  Rikitake, Yoshiyuki  ,  Hirata, Ken-ichi

6 ( 9 )  , p.e007024 , 2017-09 , Wiley
ISSN:2047998020479980
Description
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/m(2) 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(+)CD44(high)CD62L(low) 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.
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