Alpha-defensins 1-3 release by dendritic cells is reduced by estrogen.

Alpha-defensins 1-3 release by dendritic cells is reduced by estrogen.
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DOI:
10.1186/1477-7827-9-118
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发表时间:
2011-08-23
期刊:
Reproductive biology and endocrinology : RB&E
影响因子:
--
通讯作者:
Moran TM
Moran TM
中科院分区:
其他
文献类型:
--
作者:
Escribese MM;Rodríguez-García M;Sperling R;Engel SM;Gallart T;Moran TM

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在怀孕期间,母亲的免疫系统必须保护任何可能对胎儿产生负面影响的激活。感染易感性的变化以及某些自身免疫性疾病的消退代表了妊娠相关免疫改变的经验证据。性激素在怀孕期间达到极高的水平,并已被证明对许多免疫功能有直接影响,包括树突状细胞的抗病毒反应。在由单核细胞衍生的DC(MDDC)分泌的免疫活性蛋白中,有α-防御素1-3。该阳离子抗微生物肽家族具有广谱杀微生物活性,并且还显示通过吸引T细胞和未成熟DC将先天免疫与适应性免疫联系起来,T细胞和未成熟DC对于启动和极化免疫应答是必需的。我们比较了培养产生的单核细胞衍生的DC(MDDC)与直接分离的髓样树突状细胞(mDC)和浆细胞样树突状细胞(pDC),并通过ELISA测量它们在基础情况下和激素(E2或PG)处理后的α-防御素1-3分泌。此外,使用一组孕妇,我们从血液中分离mDC,并测量这些抗微生物肽沿着妊娠的水平。我们发现mDC和pDC组成性地产生α-防御素1-3,并且比MDDC产生的水平高得多。E2抑制mDC和MDDC而不是pDC的α-防御素1-3产生。PG不影响任何群体中的α-防御素1-3。此外,在40%的患者中,mDCs产生的α-防御素1-3在妊娠后期减少。在这里,我们证明了mDCs和pDCs分泌α-防御素1-3,并提出了一种新的E2对树突状细胞分泌α-防御素1-3的影响。
During pregnancy the immune system of the mother must protect any activation that may negatively affect the fetus. Changes in susceptibility to infection as well as resolution of some autoimmune disorders represent empirical evidence for pregnancy related alterations in immunity. Sex hormones reach extremely high levels during pregnancy and have been shown to have direct effects on many immune functions including the antiviral response of dendritic cells. Among the immunologically active proteins secreted by monocyte derived DCs (MDDC) are the alpha-defensins 1-3. This family of cationic antimicrobial peptides has a broad spectrum of microbicidal activity and has also been shown to link innate to adaptive immunity by attracting T cells and immature DCs, which are essential for initiating and polarizing the immune response. We compare culture-generated monocyte derived DCs (MDDCs) with directly isolated myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) and measure their alpha-defensins 1-3 secretion by ELISA both, in basal situations and after hormone (E2 or PG) treatments. Moreover, using a cohort of pregnant women we isolated mDCs from blood and also measure the levels of these anti-microbial peptides along pregnancy. We show that mDCs and pDCs constitutively produce alpha-defensins 1-3 and at much higher levels than MDDCs. Alpha-defensins 1-3 production from mDCs and MDDCs but not pDCs is inhibited by E2. PG does not affect alpha-defensins 1-3 in any of the populations. Moreover, alpha-defensins 1-3 production by mDCs was reduced in the later stages of pregnancy in 40% of the patients. Here, we demonstrate that mDCs and pDCs secrete alpha-defensins 1-3 and present a novel effect of E2 on the secretion of alpha-defensins 1-3 by dendritic cells.
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