Changes in immune cell distribution and IL-10 production are regulated through endometrial IP-10 expression in the goat uterus
Changes in immune cell distribution and IL-10 production are regulated through endometrial IP-10 expression in the goat uterus
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DOI：
10.1111/j.1600-0897.2004.00243.x
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发表时间：
2005-01-01
影响因子：
3.6
通讯作者：
Christenson, RK
中科院分区：
文献类型：
--
作者：
Imakawa, K;Nagaoka, K;Christenson, RK
问题：免疫细胞分布或重新分布的变化是妊娠建立和维持所必需的，但对于反刍动物有蹄类动物，人们对妊娠早期的这些变化知之甚少。在怀孕山羊的子宫内膜中发现了趋化因子、干扰素γ (IFN-γ) 诱导蛋白 10 kDa (IP-10、CXCL10) 的表达。在怀孕期间，子宫内膜免疫细胞的数量和/或分布及其细胞因子的产生可以通过 IP-10 进行调节。 研究方法：使用逆转录酶聚合酶链式反应 (RT-PCR)，检测 IP-10、IFN-γ、肿瘤坏死因子-α、白介素-10 (IL-10)、CXCR3 mRNA 和白细胞细胞表面标记物的表达， 研究了山羊早期妊娠期间的 CD4、CD8、CD11b 和 CD45 mRNA。使用趋化性测定证明了 IP-10 刺激外周血单核细胞 (PBMC) 迁移的能力。分别采用流式细胞术和RT-PCR研究IP-10刺激后PBMCs免疫细胞群迁移和细胞因子表达的变化。结果：妊娠山羊子宫内膜中IP-10、IL-10、CD4和CD11b mRNA水平以及CD4和CD11b阳性细胞数均高于周期性山羊子宫内膜。重组山羊 IP-10 刺激 PBMC 的迁移，使用抗 IP-10 抗体中和可显着降低该效应。在流式细胞术和 RT-PCR 分析中，IP-10 刺激的迁移细胞增加了 IL-10 和 CD11b mRNA 的表达。此外，IP-10 可以刺激 PBMC 表达 IL-10 mRNA。 结论：子宫内膜趋化因子 IP-10 可以调节表达 CD11b 的常驻细胞和可能迁移的细胞（可能是自然杀伤细胞）产生 IL-10，这些变化可能导致适合反刍动物胚胎植入的子宫免疫环境。
PROBLEM: Changes in distribution or redistribution of immune cells are required for the establishment and maintenance of pregnancy, but these changes during early pregnancy have been poorly understood in the ruminant ungulates. Expression of a chemokine, interferon-gamma (IFN-gamma)-inducible protein 10 kDa (IP-10, CXCL10), was identified in the endometrium of pregnant goats. Population and/or distribution of endometrial immune cells and their cytokine productions could be regulated by IP-10 during the period of pregnancy establishment.METHOD OF STUDY: Using reverse transcriptase-polymerase chain reaction (RT-PCR), expression of IP-10, IFN-gamma, tumor necrosis factor-alpha, interleukin-10 (IL-10), CXCR3 mRNA and leukocyte cell surface markers, CD4, CD8, CD11b and CD45 mRNA during the caprine early pregnancy was investigated. The ability of IP-10 to stimulate peripheral blood mononuclear cells (PBMCs) migration was demonstrated using a chemotaxis assay. Changes in migration of PBMCs' immune cell population and cytokine expressions with IP-10 stimulation were investigated using flow cytometry and RT-PCR respectively.RESULTS: Levels of IP-10, IL-10, CD4 and CD11b mRNA, and the number of CD4 and CD11b positive cells in pregnant goat endometrium were higher than those of cyclic goat endometrium. Migration of PBMCs was stimulated by recombinant caprine IP-10, and the effect was significantly reduced by neutralization with the use of an anti-IP-10 antibody. In the flow cytometric and RT-PCR analyses, migrated cells stimulated by IP-10 increased the expression of IL-10 and CD11b mRNA. Furthermore, IP-10 could stimulate the expression of IL-10 mRNA from PBMCs.CONCLUSION: Endometrial chemokine IP-10 could regulate IL-10 production by resident and possibly migrated cells expressing CD11b, probably natural killer cells, and these changes may result in immune environments of the uterus suitable for conceptus implantation in ruminants.