Immunoregulatory function of neonatal nucleated red blood cells in humans
Immunoregulatory function of neonatal nucleated red blood cells in humans
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DOI：
10.1016/j.imbio.2016.04.004
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发表时间：
2016-08-01
期刊：
影响因子：
2.8
通讯作者：
Hara, Toshiro
中科院分区：
文献类型：
--
作者：
Cui, Lili;Takada, Hidetoshi;Hara, Toshiro
我们发现人脐带血有核红细胞（NRBC）在先天免疫反应中具有调节功能。这些细胞抑制单核细胞响应脂多糖（LPS）产生炎性细胞因子，包括TNF-α和IL-1 β。NRBC发挥其调节功能，即使没有与单核细胞的细胞间接触。然而，在NRBC存在下通过LPS刺激的单核细胞的IL-10产生高于在NRBC不存在下培养的LPS刺激的单核细胞。添加抗IL-10受体阻断抗体可以恢复单核细胞产生炎症细胞因子，这表明与NRBC相互作用引起的单核细胞功能变化是由IL-10产生的增加介导的。全基因组微阵列分析显示，单核细胞与NRBC相互作用后表达IL-10超家族基因的量增加。作为IL-10超家族成员的IL-19增强单核细胞的IL-10产生，这表明IL-10超家族在抑制单核细胞的炎性细胞因子产生中的协同作用。据报道精氨酸酶在小鼠单核细胞中NRBC的抑制功能中起重要作用，但发现精氨酸酶在人单核细胞中没有显著作用。NRBC似乎通过诱导单核细胞产生IL-10/IL-19来抑制可能对胎儿有害的强烈先天免疫反应而具有调节作用。(C)2016 Elsevier GmbH. All rights reserved.
We found that human cord blood nucleated red blood cells (NRBCs) have a regulatory function in the innate immune reaction. These cells suppressed the production of inflammatory cytokines including TNF-alpha and IL-1 beta from monocytes in response to lipopolysaccharide (LPS). The NRBCs exerted their regulatory function even without cell-to-cell contact with the monocytes. However, IL-10 production from the monocytes by LPS stimulation in the presence of NRBCs was higher than that from LPS-stimulated monocytes cultured in the absence of NRBCs. Addition of an anti-IL-10 receptor blocking antibody restored the inflammatory cytokine production from the monocytes, suggesting that the functional change of the monocytes caused by the interaction with NRBCs was mediated by the increased IL-10 production. A whole-genome microarray analysis revealed that the monocytes expressed increased amounts of IL-10 superfamily genes after interacting with NRBCs. IL-19, which is a member of the IL-10 superfamily, enhanced IL-10 production from the monocytes, which suggested a cooperative role of the IL-10 super family in the suppression of inflammatory cytokine production from monocytes. Arginase, which was reported to play an important role in the suppressive function of NRBCs in mice monocytes, was found to have no significant role in human monocytes. The NRBCs seem to have a regulatory role through the induction of IL-10/IL-19 production by monocytes to suppress a vigorous innate immune reaction, which can be harmful to fetuses. (C) 2016 Elsevier GmbH. All rights reserved.