Therapeutic Potential of Regulatory T Cells in Preeclampsia—Opportunities and Challenges
Therapeutic Potential of Regulatory T Cells in Preeclampsia—Opportunities and Challenges
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DOI：
10.3389/fimmu.2019.00478
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发表时间：
2019-03
影响因子：
7.3
通讯作者：
S. Robertson;Ella S. Green;Alison S. Care;L. M. Moldenhauer;J. Prins;M. L. Hull;S. Barry;G. Dekker-G.-Dekke
中科院分区：
文献类型：
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作者：
S. Robertson;Ella S. Green;Alison S. Care;L. M. Moldenhauer;J. Prins;M. L. Hull;S. Barry;G. Dekker-G.-Dekke
炎症是子痫前期和其他妊娠高血压疾病的主要特征，也是导致妊娠高血压的原因之一。炎症介质和白细胞在外周血液和妊娠组织中升高，导致子宫血管异常和胎盘功能受损，尤其是严重的早发性疾病。调节性T(Treg)细胞是妊娠耐受的中心介质，并指导其他免疫细胞抗炎和促进强大的胎盘形成。Treg细胞在先兆子痫中通常受到干扰，有证据表明Treg细胞不足在症状出现之前就出现了。小鼠研究表明，从受孕开始，子宫中必须存在足够数量的具有功能的Treg细胞，以支持母亲的血管适应并防止后来的胎盘炎性病理，这是一个因果作用。因此，Treg细胞可能为先兆子痫的预防策略和治疗干预提供一个容易处理的靶点。提高Treg细胞活性的步骤需要研究，并可以纳入怀孕计划和怀孕前护理。针对自身免疫条件下的Treg细胞开发的药物干预措施值得考虑进行评估，利用严格的临床试验方法，并确保安全性至高无上。涉及体外Treg细胞生成和/或扩增的新兴细胞治疗工具迟早可能会变得相关。预防和治疗方法的成功将取决于解决几个挑战，包括开发适用于受孕前或怀孕早期的Treg细胞活性的信息性诊断测试，选择相关的患者亚组，以及确定适当的孕期进行干预。
Inflammation is a central feature and is implicated as a causal factor in preeclampsia and other hypertensive disorders of pregnancy. Inflammatory mediators and leukocytes, which are elevated in peripheral blood and gestational tissues, contribute to the uterine vascular anomalies and compromised placental function that characterize particularly the severe, early onset form of disease. Regulatory T (Treg) cells are central mediators of pregnancy tolerance and direct other immune cells to counteract inflammation and promote robust placentation. Treg cells are commonly perturbed in preeclampsia, and there is evidence Treg cell insufficiency predates onset of symptoms. A causal role is implied by mouse studies showing sufficient numbers of functionally competent Treg cells must be present in the uterus from conception, to support maternal vascular adaptation and prevent later placental inflammatory pathology. Treg cells may therefore provide a tractable target for both preventative strategies and treatment interventions in preeclampsia. Steps to boost Treg cell activity require investigation and could be incorporated into pregnancy planning and preconception care. Pharmacological interventions developed to target Treg cells in autoimmune conditions warrant consideration for evaluation, utilizing rigorous clinical trial methodology, and ensuring safety is paramount. Emerging cell therapy tools involving in vitro Treg cell generation and/or expansion may in time become relevant. The success of preventative and therapeutic approaches will depend on resolving several challenges including developing informative diagnostic tests for Treg cell activity applicable before conception or during early pregnancy, selection of relevant patient subgroups, and identification of appropriate windows of gestation for intervention.