Human trophoblasts recruited T lymphocytes and monocytes into decidua by secretion of chemokine CXCL16 and interaction with CXCR6 in the first-trimester pregnancy
Human trophoblasts recruited T lymphocytes and monocytes into decidua by secretion of chemokine CXCL16 and interaction with CXCR6 in the first-trimester pregnancy
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在妊娠早期，人类滋养层通过分泌趋化因子 CXCL16 并与 CXCR6 相互作用，将 T 淋巴细胞和单核细胞募集到蜕膜中
DOI：
10.4049/jimmunol.180.4.2367
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发表时间：
2008-02-15
影响因子：
4.4
通讯作者：
Li, Da-Jin
中科院分区：
文献类型：
--
作者：
Huang, Yu;Zhu, Xiao-Yong;Li, Da-Jin
在人类早期妊娠期间，胎儿来源的滋养层细胞在母胎界面与母体免疫细胞直接接触。在胎盘附着的部位，侵袭性绒毛外滋养层细胞遇到在蜕膜内积聚的蜕膜白细胞（DLC）。由于我们首次发现趋化因子CXCL 16在人早孕期滋养层细胞中高表达并分泌，因此本研究对胎儿滋养层细胞是否能通过分泌CXCL 16引导母体T淋巴细胞和单核细胞向蜕膜迁移的假说进行了验证。我们分析了CXCL 16在分离的早期妊娠人滋养层细胞中的转录和翻译，并检测了CXCL 16在原代培养滋养层细胞上清液中的动态分泌。我们证明了CXCL 16的唯一受体CXCR 6优先在T淋巴细胞、NKT细胞和单核细胞中表达，而在来自外周血或蜕膜的两个NK细胞亚群中几乎不表达。我们进一步证明了原代滋养层上清液中的CXCL 16对外周单核细胞和DLC的趋化活性。此外，CXCL 16/CXCR 6相互作用参与外周T淋巴细胞、γ δ T细胞和单核细胞的迁移，但不参与NKT细胞的迁移。此外，滋养层条件培养基可以选择性地富集PBMC亚群，以构成与DLC组成相似的白细胞群体，这表明胎儿来源的滋养层可以通过产生CXCL 16并与这些细胞上的CXCR 6相互作用来吸引T细胞、γ δ T细胞和单核细胞，从而在母胎界面形成专门的免疫环境。
During human early pregnancy, fetus-derived trophoblasts come into direct contact with maternal immune cells at the maternofetal interface. At sites of placental attachment, invasive extravillous trophoblasts encounter decidual leukocytes (DLC) that accumulate within the decidua. Because we first found chemokine CXCL16 was highly expressed in and secreted by the first-trimester human trophoblasts previously, in this study we tested the hypothesis of whether the fetal trophoblasts can direct migration of maternal T lymphocyte and monocytes into decidua by secreting CXCL16. We analyzed the transcription and translation of CXCL16 in the isolated first-trimester human trophoblast, and examined the kinetic secretion of CXCL16 in the supernatant of the primary-cultured trophoblasts. We demonstrated that the sole receptor of CXCL16, CXCR6, is preferentially expressed in T lymphocytes, NKT cells, and monocytes, hardly expressed in two subsets of NK cells from either the peripheral blood or decidua. We further demonstrated the chemotactic activity of CXCL16 in the supernatant of the primary trophoblast on the peripheral mononuclear cells and DLC. Moreover, the CXCL16/CXCR6 interaction is involved in the migration of the peripheral T lymphocytes, gamma delta T cells, and monocytes, but not NKT cells. In addition, the trophoblast-conditioned medium could enrich PBMC subsets selectively to constitute a leukocyte population with similar composition to that of DLC, which suggests that the fetus-derived trophoblasts can attract T cells, gamma delta T cells, and monocytes by producing CXCL16 and interaction with CXCR6 on these cells, leading to forming a specialized immune milieu at the maternofetal interface.