B-Cell Depletion Promotes Aortic Infiltration of Immunosuppressive Cells and Is Protective of Experimental Aortic Aneurysm.
B-Cell Depletion Promotes Aortic Infiltration of Immunosuppressive Cells and Is Protective of Experimental Aortic Aneurysm.
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DOI：
10.1161/atvbaha.116.307559
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发表时间：
2016-11
期刊：
影响因子：
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通讯作者：
Ailawadi G
中科院分区：
文献类型：
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作者：
Schaheen B;Downs EA;Serbulea V;Almenara CC;Spinosa M;Su G;Zhao Y;Srikakulapu P;Butts C;McNamara CA;Leitinger N;Upchurch GR Jr;Meher AK;Ailawadi G
B细胞耗竭疗法广泛用于治疗癌症和自身免疫性疾病。腹主动脉瘤 (AAA) 中 B 细胞丰富，但 B 细胞耗竭疗法是否影响 AAA 生长尚不清楚。使用小鼠 AAA 实验模型，我们旨在研究 B 细胞耗竭对 AAA 形成的影响。用小鼠单克隆抗 CD20 或对照抗体处理野生型或载脂蛋白 E 敲除小鼠，并分别进行弹性蛋白酶灌注或血管紧张素 II 输注模型以诱导 AAA。抗 CD20 抗体治疗显着耗尽了 B1 和 B2 细胞，并显着抑制了两种模型中 AAA 的生长。 B 细胞耗竭导致循环 IgM 水平降低，但不影响 IgG 水平或细胞因子/趋化因子水平。尽管抗CD20抗体处理后弹性蛋白酶灌注的主动脉中白细胞总数保持不变，但B细胞亚型的数量显着降低。有趣的是，在 B 细胞耗尽小鼠的主动脉中检测到表达免疫调节酶吲哚 2,3-双加氧酶 (IDO) 的浆细胞样树突状细胞 (pDC)。随着 IDO+ pDC 的增加，B 细胞耗竭小鼠的主动脉中调节性 T 细胞的数量较高，而促炎基因的表达较低。在共培养模型中，B 细胞的存在显着降低了 IDO+ pDC 的数量，但不影响 pDC 总数。目前的结果表明，B 细胞耗竭可以保护小鼠免受实验性 AAA 形成的影响，并促进主动脉中免疫抑制环境的出现。
B cell depletion therapy is widely used for treatment of cancers and autoimmune diseases. B cells are abundant in abdominal aortic aneurysms (AAA), however, it is unknown whether B cell depletion therapy affects AAA growth. Using experimental models of murine AAA, we aim to examine the effect of B cell depletion on AAA formation. Wild-type or Apolipoprotein E knockout mice were treated with mouse monoclonal anti-CD20 or control antibodies and subjected to an elastase perfusion or angiotensin II-infusion model to induce AAA, respectively. Anti-CD20 antibody treatment significantly depleted B1 and B2 cells, and strikingly suppressed AAA growth in both models. B cell depletion resulted in lower circulating IgM levels, but did not affect the levels of IgG or cytokine/chemokine levels. Although the total number of leukocyte remained unchanged in elastase perfused aortas following anti-CD20 antibody treatment, the number of B cell subtypes was significantly lower. Interestingly, plasmacytoid dendritic cells (pDCs) expressing the immunomodulatory enzyme indole 2,3-dioxygenase (IDO) were detected in the aortas of B cell depleted mice. In accordance with an increase in IDO+ pDCs, the number of regulatory T cells was higher while the expression of pro-inflammatory genes was lower in aortas of B cell depleted mice. In a coculture model, presence of B cells significantly lowered the number of IDO+ pDCs without affecting total pDC number. The present results demonstrate that B cell depletion protects mice from experimental AAA formation and promotes emergence of an immunosuppressive environment in aorta.