Intra-amniotic IL-1β induces fetal inflammation in rhesus monkeys and alters the regulatory T cell/IL-17 balance.
Intra-amniotic IL-1β induces fetal inflammation in rhesus monkeys and alters the regulatory T cell/IL-17 balance.
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DOI：
10.4049/jimmunol.1300270
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发表时间：
2013-08-01
期刊：
影响因子：
--
通讯作者：
Chougnet CA
中科院分区：
文献类型：
--
作者：
Kallapur SG;Presicce P;Senthamaraikannan P;Alvarez M;Tarantal AF;Miller LM;Jobe AH;Chougnet CA
极低出生体重早产儿易患致衰弱性炎性疾病，其中许多与绒毛膜炎有关。为了确定绒毛膜炎对胎儿免疫系统的影响，在恒河猴妊娠80%时经子宫内给予IL-1β。IL-1β引起组织学绒毛膜炎以及肺部炎症（胎儿气道中中性粒细胞或单核细胞浸润）。给药后24 h，肺中多种促炎细胞因子mRNA大幅增加，在72 h时相对于对照组仍保持升高。羊膜内IL-1β也诱导肺表面活性蛋白的持续表达。重要的是，IL-1β显著改变了炎性和调节性T细胞（Treg细胞）之间的平衡。IL-1β注射后24 h，淋巴器官中CD 3 + CD 4 + FOXP 3 + T细胞的频率降低。相反，淋巴器官中IL-17 A产生细胞（CD 3 + CD 4+、CD 3 + CD 4 −和CD 3 − CD 4 −亚群）增加。IFN-γ表达细胞的频率没有变化。在这种单次暴露于炎症触发物的模型中，与对照组相比，CD 3 + CD 4 + FOXP 3+细胞迅速反弹，并且在72 h时其频率增加。IL-17表达也是短暂的。有趣的是，T细胞谱的改变仅限于淋巴器官，而不是循环胎儿T细胞。总之，这些结果表明绒毛膜炎诱导的IL-1/IL-17轴参与了早产新生儿可能发生的严重炎症。加强Treg细胞和/或控制IL-17可以提供改善这些异常的手段。
Very low birth weight preterm newborns are susceptible to the development of debilitating inflammatory diseases, many of which are associated with chorioamnionitis. To define the effects of chorioamnionitis on the fetal immune system, IL-1β was administered intra-amniotically at ∼80% gestation in rhesus monkeys. IL-1β caused histological chorioamnionitis as well as lung inflammation (infiltration of neutrophils or monocytes in the fetal airways). There were large increases of multiple pro-inflammatory cytokine mRNAs in the lungs 24 h post-administration, which remained elevated relative to controls at 72 h. Intra-amniotic IL-1β also induced sustained expression of the surfactant proteins in the lungs. Importantly, IL-1β significantly altered the balance between inflammatory and regulatory T cells (Treg cells). Twenty-four h after IL-1β injection, the frequency of CD3+CD4+FOXP3+ T cells was decreased in lymphoid organs. In contrast, IL-17A–producing cells (CD3+CD4+, CD3+CD4−, and CD3−CD4− subsets) were increased in lymphoid organs. The frequency of IFN-γ-expressing cells did not change. In this model of a single exposure to an inflammatory trigger, CD3+CD4+FOXP3+ cells rebounded quickly and their frequency was increased at 72 h compared to controls. IL-17 expression was also transient. Interestingly, the T cell profile alteration was confined to the lymphoid organs and not to circulating fetal T cells. Together, these results suggest the chorioamnionitis-induced IL-1/IL-17 axis is involved in the severe inflammation that can develop in preterm newborns. Boosting Treg cells and/or controlling IL-17 may provide a means to ameliorate these abnormalities.
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作者：
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DOI：
10.1152/ajplung.2001.280.3.l527
发表时间：
2001-03-01
影响因子：
4.9
作者：
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通讯作者：
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