Increase in complement iC3b is associated with anti-inflammatory cytokine expression during late pregnancy in mice.
Increase in complement iC3b is associated with anti-inflammatory cytokine expression during late pregnancy in mice.
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DOI：
10.1371/journal.pone.0178442
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Imakawa K
中科院分区：
文献类型：
--
作者：
Nakamura K;Kusama K;Bai R;Ishikawa S;Fukushima S;Suda Y;Imakawa K
胎儿同种异体移植物和母亲之间的免疫耐受对于妊娠的建立和维持至关重要;然而，这些机制，特别是妊娠后期的机制尚未明确阐明。本研究的目的是检查先天免疫特性的存在和潜在的功能，以中晚期妊娠。我们首先使用2D-PAGE，随后通过MALDI-TOF/MS分析来表征来自妊娠第11天（P11）小鼠的蜕膜中的上调蛋白。这些分析确定了P11蜕膜中补体成分3（C3）及其衍生物的增加。然后我们发现，在蜕膜组织中，C3 mRNA在P15时增加，并在P19时保持较高水平。补体成分因子I（Cfi）和补体受体1样蛋白（Crry）将C3转化为C3 b，然后转化为iC 3b，这两种蛋白都存在于P19胎盘中。此外，在蜕膜和胎盘组织中的iC 3b蛋白及其受体CR 3（Cd 11b/Cd 18）在妊娠后期增加。此外，CR 3亚基CD 11b蛋白主要定位于P19胎盘的海绵滋养层。由于已知iC 3b可诱导抗炎细胞因子产生，因此将分析扩展至检查促炎和抗炎细胞因子IL 12、IL 10和Tgfb 1的变化。IL 12在P15和P19胎盘组织中表达降低，IL 10和Tgfb 1在P19胎盘组织中表达增高。此外，当用抗C3抗体处理妊娠小鼠时，胎盘IL 10和Tgfb 1 mRNA下调，检测C3，C3 b和iC 3b。这些结果表明，C3衍生物，特别是iC 3b及其受体CR 3在胎儿-母体界面上调，并表明iC 3b可能调节胎盘表达的抗炎细胞因子，IL 10和TGFB 1，在妊娠后期。
Immunological tolerance between fetal allograft and mother is crucial for pregnancy establishment and maintenance; however, these mechanisms particularly those during the latter part of pregnancy have not been definitively elucidated. The aim of this study was to examine the presence and potential function of innate immunity characteristic to the middle to late pregnancy. We first characterized up-regulated proteins in decidua from day 11 pregnant (P11) mice using 2D-PAGE, followed by MALDI-TOF/MS analysis. These analyses identified increased complement component 3 (C3) and its derivatives in P11 decidua. We then found that in the decidual tissues, C3 mRNA increased on P15 and remained high on P19. C3 is converted to C3b and then iC3b by complement component factor I (Cfi) and complement receptor 1-like protein (Crry), both of which were present in P19 placentas. In addition, iC3b proteins and its receptor CR3 (Cd11b/Cd18) in decidual and placental tissues increased toward the latter phase of pregnancy. Moreover, CR3 subunit CD11b protein was predominantly localized to spongiotrophoblast layer in the P19 placenta. Because iC3b is known to induce anti-inflammatory cytokine production, the analysis was extended to examine changes in pro- and anti-inflammatory cytokines, Il12, Il10, and Tgfb1. Il12 expression decreased in P15 and P19 placenta, while high mRNA expression of Il10 and Tgfb1 was found in P19 placental tissues. Furthermore, placental Il10 and Tgfb1 mRNAs were down-regulated when pregnant mice were treated with an anti-C3 antibody, detecting C3, C3b and iC3b. These results indicated that C3 derivatives, in particular, iC3b and its receptor CR3 were up-regulated at the fetal-maternal interface, and suggest that iC3b may regulate the placental expression of anti-inflammatory cytokines, IL10 and TGFB1, during the latter phase of pregnancy.