Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Łukasiewicz Research Network - PORT Polish Center for Technology Development, Stablowicka 147 Str., Wroclaw, Poland.
Sci Rep. 2020 Jun 29;10(1):10531. doi: 10.1038/s41598-020-66957-z.
The imbalance in immune tolerance may cause the variety of reproductive failures. An intravenous immunoglobulin infusion (IVIg) therapy is used to improve the live birth rate in women suffering from recurrent pregnancy loss, recurrent spontaneous abortions and recurrent implantation failures. However, the results of IVIg studies are still inconclusive as IVIg infusion in women suffering from pregnancy loss is sometimes ineffective. One of the mechanisms of action of this treatment is inhibition of B cells differentiation and expansion of Tregs and secretion of interleukin 10. It was proposed that immunomodulatory effects of IVIg may be attributed to tregitopes - self-IgG-derived epitopes present in the structure of immunoglobulins. Similarly to IVIg, tregitopes cause the expansion of Tregs and secretion of antigen-specific effector cytokine response. Here, we studied whether the administration of mouse tregitope 167 and/or 289 can prevent abortions in mouse abortion-prone mouse matings. We revealed that tregitopes reduce the foetal death rate. This may be driven by observed higher pool of peripheral Tregs, increased production of IL-10 by Tregs and Bregs and/or maintaining the tolerogenic phenotype of antigen-presenting cells. We believe that our findings may indicate a potential alternative to IVIg for therapeutic intervention in case of pregnancy failures.
免疫耐受失衡可能导致各种生殖失败。静脉注射免疫球蛋白（IVIg）治疗用于提高复发性妊娠丢失、反复自然流产和反复着床失败患者的活产率。然而，IVIg 研究的结果仍不确定，因为 IVIg 输注对妊娠丢失的女性有时无效。这种治疗的作用机制之一是抑制 B 细胞分化和 Treg 的扩增以及白细胞介素 10 的分泌。有人提出，IVIg 的免疫调节作用可能归因于 tregitopes-存在于免疫球蛋白结构中的自身 IgG 衍生表位。与 IVIg 类似，tregitopes 导致 Treg 的扩增和抗原特异性效应细胞因子反应的分泌。在这里，我们研究了给予小鼠 tregitope 167 和/或 289 是否可以预防易流产小鼠交配中的流产。我们发现 tregitopes 降低了胎儿死亡率。这可能是由于观察到外周 Treg 池增加、Treg 和 Breg 产生的 IL-10 增加和/或维持抗原呈递细胞的耐受表型所致。我们相信，我们的发现可能表明在妊娠失败的情况下，IVIg 治疗干预的潜在替代方法。
