Heme oxygenase and the immune system in normal and pathological pregnancies.
Heme oxygenase and the immune system in normal and pathological pregnancies.
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DOI：
10.3389/fphar.2015.00084
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发表时间：
2015
影响因子：
5.6
通讯作者：
Stevenson DK
中科院分区：
文献类型：
--
作者：
Ozen M;Zhao H;Lewis DB;Wong RJ;Stevenson DK
正常妊娠是一种免疫耐受状态。许多因素，包括环境，社会经济，遗传和感染和/或其他炎症原因引起的免疫变化，可能导致个体间差异，导致正常或病理性妊娠。特别是，免疫系统的失衡可能导致许多妊娠相关疾病，如不孕症，流产，先兆子痫和早产，导致母亲/胎儿死亡，早产或小于胎龄新生儿。新的研究结果表明，髓系调节细胞和调节性T细胞（T细胞）可能介导正常妊娠期间的免疫耐受。相反，效应T细胞（Tefs）被认为是导致不良妊娠结局的原因。此外，胎儿-母体耐受性影响发育中的胎儿。已经显示Treg/Teff平衡影响同窝仔数，并且妊娠诱导的Teff的过继转移可以防止小鼠中的胎儿排斥。血红素加氧酶-1（HO-1）通过其抗炎、抗凋亡、抗氧化和抗增殖作用在许多疾病中具有保护作用。HO-1在胎盘中高度表达，并在血管生成和胎盘血管发育以及调节妊娠中的血管张力中起作用。此外，HO-1通过介导先天性和适应性免疫系统之间的串扰是免疫稳态的主要调节剂。此外，HO-1可以抑制炎症诱导的免疫效应细胞的表型成熟和促炎细胞因子的分泌，并促进抗炎细胞因子的产生。HO-1也可能与T细胞活化相关，并可通过促进效应子应答的Treg抑制来限制基于免疫的组织损伤。因此，HO-1及其副产物可以通过其免疫调节作用防止妊娠并发症，并且HO-1或其下游作用的调节具有预防或治疗妊娠并发症和早产的潜力。
Normal pregnancy is an immunotolerant state. Many factors, including environmental, socioeconomic, genetic, and immunologic changes by infection and/or other causes of inflammation, may contribute to inter-individual differences resulting in a normal or pathologic pregnancy. In particular, imbalances in the immune system can cause many pregnancy-related diseases, such as infertility, abortions, pre-eclampsia, and preterm labor, which result in maternal/fetal death, prematurity, or small-for-gestational age newborns. New findings imply that myeloid regulatory cells and regulatory T cells (Tregs) may mediate immunotolerance during normal pregnancy. Effector T cells (Teffs) have, in contrast, been implicated to cause adverse pregnancy outcomes. Furthermore, feto-maternal tolerance affects the developing fetus. It has been shown that the Treg/Teff balance affects litter size and adoptive transfer of pregnancy-induced Tregs can prevent fetal rejection in the mouse. Heme oxygenase-1 (HO-1) has a protective role in many conditions through its anti-inflammatory, anti-apoptotic, antioxidative, and anti-proliferative actions. HO-1 is highly expressed in the placenta and plays a role in angiogenesis and placental vascular development and in regulating vascular tone in pregnancy. In addition, HO-1 is a major regulator of immune homeostasis by mediating crosstalk between innate and adaptive immune systems. Moreover, HO-1 can inhibit inflammation-induced phenotypic maturation of immune effector cells and pro-inflammatory cytokine secretion and promote anti-inflammatory cytokine production. HO-1 may also be associated with T-cell activation and can limit immune-based tissue injury by promoting Treg suppression of effector responses. Thus, HO-1 and its byproducts may protect against pregnancy complications by its immunomodulatory effects, and the regulation of HO-1 or its downstream effects has the potential to prevent or treat pregnancy complications and prematurity.