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人绒毛膜促性腺激素促进小鼠调节性 T 细胞的产生并限制妊娠相关致炎型 Th17 反应。

Human chorionic gonadotropin promotes murine Treg cells and restricts pregnancy-harmful proinflammatory Th17 responses.

机构信息

Experimental Obstetrics and Gynecology, Medical Faculty, Health Campus Immunology, Infectilogy and Inflammation (GC-I3), Otto-von-Guericke University, Magdeburg, Germany.

Department of Environmental Immunology, Helmholtz Centre for Environmental Research, Leipzig, Germany.

出版信息

Front Immunol. 2022 Sep 20;13:989247. doi: 10.3389/fimmu.2022.989247. eCollection 2022.

DOI:10.3389/fimmu.2022.989247
PMID:36203576
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9531259/
Abstract

An equilibrium between proinflammatory and anti-inflammatory immune responses is essential for maternal tolerance of the fetus throughout gestation. To study the participation of fetal tissue-derived factors in this delicate immune balance, we analyzed the effects of human chorionic gonadotropin (hCG) on murine Treg cells and Th17 cells , and on pregnancy outcomes, fetal and placental growth, blood flow velocities and remodeling of the uterine vascular bed . Compared with untreated CD4CD25 T cells, hCG increased the frequency of Treg cells upon activation of the LH/CG receptor. hCG, with the involvement of IL-2, also interfered with induced differentiation of CD4 T cells into proinflammatory Th17 cells. In already differentiated Th17 cells, hCG induced an anti-inflammatory profile. Transfer of proinflammatory Th17 cells into healthy pregnant mice promoted fetal rejection, impaired fetal growth and resulted in insufficient remodeling of uterine spiral arteries, and abnormal flow velocities. Our works show that proinflammatory Th17 cells have a negative influence on pregnancy that can be partly avoided by re-programming of proinflammatory Th17 cells with hCG.

摘要

在整个妊娠期，促炎和抗炎免疫反应之间的平衡对于母体对胎儿的耐受至关重要。为了研究胎儿组织来源的因子在这种微妙的免疫平衡中的参与作用，我们分析了人绒毛膜促性腺激素（hCG）对小鼠 Treg 细胞和 Th17 细胞的影响，以及对妊娠结局、胎儿和胎盘生长、血流速度和子宫血管床重塑的影响。与未经处理的 CD4CD25 T 细胞相比，hCG 通过激活 LH/CG 受体增加了 Treg 细胞的频率。hCG 还通过涉及 IL-2 来干扰 CD4 T 细胞向促炎 Th17 细胞的诱导分化。在已经分化的 Th17 细胞中，hCG 诱导出抗炎表型。将促炎 Th17 细胞转移到健康妊娠的小鼠中会促进胎儿排斥，损害胎儿生长，并导致子宫螺旋动脉重塑不足和血流速度异常。我们的研究表明，促炎 Th17 细胞对妊娠有负面影响，但可以通过 hCG 对促炎 Th17 细胞进行重新编程来部分避免。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f7/9531259/f0339296947a/fimmu-13-989247-g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f7/9531259/f0339296947a/fimmu-13-989247-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f7/9531259/62984da9fbfa/fimmu-13-989247-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f7/9531259/9f5724b83f78/fimmu-13-989247-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f7/9531259/a7b1d66eb733/fimmu-13-989247-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f7/9531259/6f69d36d295d/fimmu-13-989247-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f7/9531259/7fe140f828c3/fimmu-13-989247-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f7/9531259/113df2316d58/fimmu-13-989247-g008.jpg
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