Progesterone and autoimmune disease.
Progesterone and autoimmune disease.
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DOI：
10.1016/j.autrev.2011.12.003
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发表时间：
2012-05
影响因子：
13.6
通讯作者：
Hughes, Grant C.
中科院分区：
文献类型：
--
作者：
Hughes, Grant C.
人类免疫系统的性别二态性在某些自身免疫性疾病（AD）如系统性红斑狼疮（SLE）的女性优势中最为明显。流行病学，观察和实验证据强烈表明性类固醇是人类AD遗传风险的重要调节剂。在这方面，孕激素（Pg），一种免疫调节性雌性类固醇的作用，知之甚少。几条调查线表明Pg和合成孕激素以不同的方式影响AD和免疫介导的损伤的风险，这取决于它们的浓度和它们对免疫器官、免疫细胞或免疫攻击靶向的组织中表达的各种Pg受体的参与。在低生理水平下，Pg可增强在SLE发病机制中重要的干扰素-α（IFN-α）途径。常用的合成孕激素可能有相反的效果。在妊娠水平，Pg可以通过抑制辅助性T细胞1型（Th 1）和Th 17通路以及诱导抗炎分子来抑制类风湿性关节炎（RA）和多发性硬化症（MS）的疾病活动。重要的是，Pg的免疫调节作用不同于雌激素和雄激素。另一层复杂性来自性激素信号通路的明显相互依赖。确定Pg和其他性类固醇调节AD和免疫介导的损伤风险的机制将需要澄清其体内的细胞和分子靶点。这些未来的研究应该了解人类AD的最新遗传发现，特别是那些揭示其性别特异性遗传关联的发现。
Sexual dimorphism in human immune systems is most apparent in the female predominance of certain autoimmune diseases (ADs) like systemic lupus erythematosus (SLE). Epidemiologic, observational and experimental evidence strongly suggest sex steroids are important modulators of genetic risk in human AD. In this regard, the roles of progesterone (Pg), an immunomodulatory female sex steroid, are poorly understood. Several lines of investigation indicate Pg and synthetic progestins impact risk of AD and immune-mediated injury in different ways depending on their concentrations and their engagement of various Pg receptors expressed in immune organs, immune cells or tissues targeted by immune attack. At low physiologic levels, Pg may enhance interferon-alpha (IFN-α) pathways important in SLE pathogenesis. Commonly used synthetic progestins may have the opposite effect. At pregnancy levels, Pg may suppress disease activity in rheumatoid arthritis (RA) and multiple sclerosis (MS) via inhibition of T helper type 1 (Th1) and Th17 pathways and induction of anti-inflammatory molecules. Importantly, Pg’s immunomodulatory effects differ from those of estrogens and androgens. An additional layer of complexity arises from apparent interdependence of sex hormone signaling pathways. Identifying mechanisms by which Pg and other sex steroids modulate risk of AD and immune-mediated injury will require clarification of their cellular and molecular targets in vivo. These future studies should be informed by recent genetic discoveries in human AD, particularly those revealing their sex-specific genetic associations.
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影响因子：
5.1
作者：
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通讯作者：
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影响因子：
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作者：
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发表时间：
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