Evidence that interferon-tau secreted from Day-7 embryo in vivo generates anti-inflammatory immune response in the bovine uterus
Evidence that interferon-tau secreted from Day-7 embryo in vivo generates anti-inflammatory immune response in the bovine uterus
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DOI：
10.1016/j.bbrc.2018.04.178
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发表时间：
2018-06-12
影响因子：
3.1
通讯作者：
Miyamoto, Akio
中科院分区：
文献类型：
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作者：
Rashid, Mohammad B.;Talukder, Anup K.;Miyamoto, Akio
最近的研究表明，第7天的牛胚胎开始与子宫上皮细胞通过干扰素-tau（IFNT）信号转导。然而，IFNT在胚胎刚从输卵管移出后子宫中的免疫调节作用尚不清楚。我们的目的是检验这一假设，即第7天的牛胚胎分泌IFNT在子宫中，诱导抗炎反应的免疫细胞。从第-7天供体妊娠母牛收集具有多个胚胎的子宫冲洗液（UF），然后在UF中培养外周血单个核细胞（PBMC）。在PBMC中检测到的转录本显示，与来自非妊娠奶牛的UF相比，来自妊娠奶牛的UF下调促炎细胞因子（TNFA，IL 1B）和上调抗炎细胞因子（IL 10）的表达，并激活干扰素刺激的基因（ISG，ISG 15，OAS 1）。在UF中加入特异性抗IFNT抗体可抑制对PBMC的作用，表明IFNT是这种免疫调节的主要因素。来自牛子宫上皮细胞的条件培养基在体外用IFNT刺激和补充有新鲜IFNT两者的观察结果诱导相似的PBMC基因表达，证实IFNT直接作用于这种免疫串扰。本研究表明，第7天胚胎在体内分泌的IFNT在免疫细胞中产生抗炎反应，这可能提供免疫耐受以接受胚胎。(C)2018爱思唯尔公司All rights reserved.
Recent studies suggest that Day-7 bovine embryo starts to communicate with the uterine epithelium through interferon-tau (IFNT) signaling. However, immune modulatory role of IFNT in the uterus just after the embryo moves from the oviduct is unclear. We aimed to examine the hypothesis that Day-7 bovine embryo secretes IFNT in the uterus, which induces anti-inflammatory response in immune cells. The uterine flush (UF) with multiple embryos was collected from Day-7 donor pregnant cows and peripheral blood mononuclear cells (PBMCs) were then cultured in UF. Transcripts detected in PBMCs revealed that UF from pregnant cows down-regulated pro-inflammatory cytokines (TNFA, IL1B) and upregulated anti-inflammatory cytokine (IL10) expression, with activation of interferon-stimulated genes (ISGs, ISG15, OAS1) as compared with UF from non-pregnant cows. An addition of specific anti-IFNT antibody to the UF inhibited the effect on PBMCs, indicating that IFNT is a major factor for such immune modulation. The observation that conditioned media from bovine uterine epithelial cells both stimulated with IFNT in vitro and supplemented with fresh IFNT induced similar PBMCs gene expression, confirming that IFNT directly acts on this immune crosstalk. This study shows that IFNT secreted from Day-7 embryo in vivo generates anti-inflammatory response in immune cells, which may provide immunological tolerance to accept the embryo. (C) 2018 Elsevier Inc. All rights reserved.