Estriol generates tolerogenic dendritic cells in vivo that protect against autoimmunity.
Estriol generates tolerogenic dendritic cells in vivo that protect against autoimmunity.
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DOI：
10.4049/jimmunol.1001322
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发表时间：
2011-03-15
期刊：
影响因子：
--
通讯作者：
Whitacre CC
中科院分区：
文献类型：
--
作者：
Papenfuss TL;Powell ND;McClain MA;Bedarf A;Singh A;Gienapp IE;Shawler T;Whitacre CC
慢性炎症会导致多种疾病，而炎症的调节对于疾病的控制和解决至关重要。性激素具有强大的免疫调节能力。具体来说，雌激素会影响免疫细胞和炎症，从而导致自身免疫的性别二态性，并预防多发性硬化症 (MS) 及其动物模型实验性自身免疫性脑脊髓炎 (EAE) 怀孕期间出现的疾病。尽管长期以来人们认为主要作用于 T 细胞，但最近的证据表明，树突状细胞 (DC) 等骨髓细胞对于介导雌激素的保护作用至关重要。雌三醇 (E3) 是一种妊娠特异性雌激素，对 MS 和 EAE 具有治疗功效，我们评估了 E3 是否可以仅通过 DC 发挥作用，以预防炎症性自身免疫性疾病 EAE。 E3 DC 中激活标记物（CD80 和 CD86）和抑制性共刺激标记物（PD-L1、PD-L2、B7-H3 和 B7-H4）的水平增加。 E3 DC 降低了促炎性 IL-12、IL-23 和 IL-6 mRNA 表达，增加了免疫调节性 IL-10 和 TGF-β mRNA 表达，并降低了 IL-12/IL-10 蛋白产量的比率。重要的是，在主动诱导 EAE 之前将 E3 DC 转移至小鼠体内，可防止小鼠因免疫偏离 Th2 反应而发生 EAE。即使面对体外和体内炎症挑战，这种保护作用也是显而易见的。总之，我们的结果表明 E3 产生耐受性 DC，可预防炎症性自身免疫性疾病 EAE。利用免疫调节疗法（例如 E3）靶向产生耐受性 DC，在治疗多种自身免疫性疾病和慢性炎症性疾病方面具有潜在应用。
Chronic inflammation contributes to numerous diseases, and regulation of inflammation is crucial for disease control and resolution. Sex hormones have potent immunoregulatory abilities. Specifically, estrogen influences immune cells and inflammation, which contributes to the sexual dimorphism of autoimmunity and protection against disease seen during pregnancy in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Although long thought to act primarily on T cells, recent evidence demonstrated that myeloid cells, such as dendritic cells (DCs), are essential in mediating estrogen's protective effects. Estriol (E3), a pregnancy-specific estrogen, has therapeutic efficacy in MS and EAE, and we evaluated whether E3 could act exclusively through DCs to protect against the inflammatory autoimmune disease EAE. Levels of activation markers (CD80 and CD86) and inhibitory costimulatory markers (PD-L1, PD-L2, B7–H3, and B7–H4) were increased in E3 DCs. E3 DCs had decreased proinflammatory IL-12, IL-23, and IL-6 mRNA expression, increased immunoregulatory IL-10 and TGF-β mRNA expression, and a decreased ratio of IL-12/IL-10 protein production. Importantly, transfer of E3 DCs to mice prior to active induction of EAE protected them from developing EAE through immune deviation to a Th2 response. This protection was apparent, even in the face of in vitro and in vivo inflammatory challenge. In summary, our results showed that E3 generates tolerogenic DCs, which protect against the inflammatory autoimmune disease EAE. Targeted generation of tolerogenic DCs with immunomodulatory therapeutics, such as E3, has potential applications in the treatment of numerous autoimmune and chronic inflammatory diseases.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
32.4
作者：
Jung, S;Unutmaz, D;Lang, RA
通讯作者：
Lang, RA
影响因子：
5.5
作者：
Du, CG;Sriram, S
通讯作者：
Sriram, S
DOI：
10.1196/annals.1286.031
发表时间：
2003-01-01
期刊：
STEROIDS AND THE NERVOUS SYSTEM
影响因子：
--
作者：
Drew, PD;Chavis, JA;Bhatt, R
通讯作者：
Bhatt, R
影响因子：
82.9
作者：
Figdor, CG;de Vries, IJM;Melief, CJM
通讯作者：
Melief, CJM