Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
Department of Gynaecology, Leiden University Medical Center, Leiden, the Netherlands.
J Reprod Immunol. 2020 Feb;137:103076. doi: 10.1016/j.jri.2019.103076. Epub 2019 Dec 24.
Dendritic cells (DCs) are key in shaping immune responses and are recruited to the human cervix after coitus by seminal plasma (SP). SP has been shown to skew the differentiation of monocyte-derived DCs towards an anti-inflammatory profile when cultured in medium containing fetal calf serum (FCS). Here, we confirmed that SP skewed DCs cultured in fetal bovine serum (FBS) towards a tolerogenic profile. To create a setting more similar to the in vivo situations in humans, we tested the immune regulatory effect of SP on DCs in cell cultures containing human serum (HS). SP-DCs cultured in HS did show increased CD14 and decreased CD1a, indicating an inhibited maturation phenotype. Gene expression of TGF-β and IL-10 and IL-10 protein expression were elevated in LPS-activated SP-DCs, whereas IL-12p70 protein levels were decreased compared to LPS-activated control DCs. In contrast to FBS culture conditions, in the presence of HS co-cultures of SP-DCs with allogeneic peripheral blood mononuclear cells (PBMCs) did not result in decreased T cell proliferation and inflammatory cytokine production. Thus, under HS culture conditions SP can skew the differentiation of monocyte-derived DCs phenotypically towards alternatively activated DCs, but this immune regulatory phenotype is functionally less pronounced compared to SP-treated DCs cultured in FBS containing medium. These findings highlight the importance of the source of the serum that is used in SP treated cell cultures in vitro.
树突状细胞(DCs)在塑造免疫反应方面起着关键作用,在性交后会被精液(SP)招募到人体宫颈。当在含有胎牛血清(FCS)的培养基中培养时,SP 已被证明会使单核细胞来源的 DC 向抗炎表型分化。在这里,我们证实 SP 会使在胎牛血清(FBS)中培养的 DC 向耐受表型倾斜。为了创造一个更类似于人类体内情况的环境,我们在含有人血清(HS)的细胞培养物中测试了 SP 对 DC 的免疫调节作用。在 HS 中培养的 SP-DC 确实显示出 CD14 的增加和 CD1a 的减少,表明其成熟表型受到抑制。LPS 激活的 SP-DC 中 TGF-β 和 IL-10 的基因表达以及 IL-10 蛋白表达升高,而与 LPS 激活的对照 DC 相比,IL-12p70 蛋白水平降低。与 FBS 培养条件相反,在 HS 共培养物中,SP-DC 与同种异体外周血单核细胞(PBMC)共培养不会导致 T 细胞增殖和炎症细胞因子产生减少。因此,在 HS 培养条件下,SP 可以使单核细胞来源的 DC 表型向替代激活的 DC 分化,但与在含有 FBS 的培养基中培养的 SP 处理的 DC 相比,这种免疫调节表型在功能上不那么明显。这些发现强调了在体外 SP 处理的细胞培养中使用的血清来源的重要性。