Redzovic Arnela, Gulic Tamara, Laskarin Gordana, Eminovic Senija, Haller Herman, Rukavina Daniel
Department of Radiotherapy and Oncology, Clinical Hospital Centre Rijeka, Rijeka, Croatia.
Department of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia.
Am J Reprod Immunol. 2015 Jul;74(1):38-53. doi: 10.1111/aji.12374. Epub 2015 Mar 4.
The aim of the study was to assess possible binding of a mixture of constitutive Hsc70 and inducible Hsp70 forms (HSP70) to Toll-like receptor (TLR) 4 and CD91 receptors on decidual CD1a(+) dendritic cells (DCs) and their influence on DCs maturation status.
Immunohistology and immunofluorescence of paraffin-embedded first trimetester and term pregnancy decidua were performed together with flow cytometry detection of antigens in DCs after stimulation of decidual mononuclear cells with HSP70.
Hsc70 and Hsp70 labeling revealed intracellular and nuclear staining in trophoblast cells. The numbers of Hsc70(+) and Hsp70(+) cells of decidual tissue were higher in early pregnancy decidua than in decidua at term. HSP70 binds CD91 and TLR4 receptors on CD1a(+) DCs and increased the expression of CD83, HLA-DR, CD80, and CD86, but decreased CC receptor (CCR) 5. HSP70 increased CC ligand (CCL) 3 and CCL22. HSP70 in the concentration of 1 μg/mL increased the percentage of interferon-γ and interleukin (IL)-15-expressing cells over the cells expressing IL-4.
HSP70 binds CD91 and TLR4 on decidual CD1a(+) DCs, causes their maturation, and increases IL-15 in the context of Th1 cytokine/chemokine domination, which could support immune response harmful for ongoing pregnancy.
本研究的目的是评估组成型Hsc70和诱导型Hsp70形式的混合物（HSP70）与蜕膜CD1a(+)树突状细胞（DCs）上的Toll样受体（TLR）4和CD91受体的可能结合及其对DCs成熟状态的影响。
对石蜡包埋的孕晚期和足月妊娠蜕膜进行免疫组织学和免疫荧光检查，并在用HSP70刺激蜕膜单核细胞后通过流式细胞术检测DCs中的抗原。
Hsc70和Hsp70标记显示滋养层细胞内和细胞核有染色。早孕蜕膜中蜕膜组织的Hsc70(+)和Hsp70(+)细胞数量高于足月蜕膜。HSP70与CD1a(+) DCs上的CD91和TLR4受体结合，增加了CD83、HLA-DR、CD80和CD86的表达，但降低了CC受体（CCR）5。HSP70增加了CC配体（CCL）3和CCL22。浓度为1μg/mL的HSP70增加了表达干扰素-γ和白细胞介素（IL）-15的细胞百分比，高于表达IL-4的细胞。
HSP70与蜕膜CD1a(+) DCs上的CD91和TLR4结合，使其成熟，并在Th1细胞因子/趋化因子占主导的情况下增加IL-15，这可能支持对正在进行的妊娠有害的免疫反应。
