IL-10 producing B cells rescue mouse fetuses from inflammation-driven fetal death and are able to modulate T cell immune responses
IL-10 producing B cells rescue mouse fetuses from inflammation-driven fetal death and are able to modulate T cell immune responses
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DOI：
10.1038/s41598-019-45860-2
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发表时间：
2019-06-27
影响因子：
4.6
通讯作者：
Zenclussen, Ana Claudia
中科院分区：
文献类型：
--
作者：
Busse, Mandy;Campe, Kim-Norina Jutta;Zenclussen, Ana Claudia
了解导致孕妇亚临床感染后胎儿死亡的机制对于制定新的治疗策略至关重要。在这里，我们讨论了IL-10分泌B细胞（B10）在维持妊娠期间免疫平衡中的相关性。缺乏成熟B细胞的mu MT雌性妊娠正常，尽管它们的胎儿更小，Treg池不像B细胞充足的对照组那样扩大。怀孕的mu MT雌性尽管Treg较少，但对LPS更敏感；它们的胎儿在与WT动物妊娠相适应的剂量下死亡。过继移植IL-10阴性B效应细胞或来自IL-10缺陷小鼠的B细胞没有改变这一结果。B10细胞的转移或重组小鼠IL-10的应用减少了胎儿的损失，这与Treg数量的正常化和胎母界面的细胞因子调节有关。B细胞源性IL-10抑制T细胞产生IL-17A和IL-6，促进幼稚细胞向Treg的转化。当炎症信号干扰时，需要B10细胞来恢复胎母界面的免疫平衡。我们的数据表明，B细胞在维持怀孕期间免疫和耐受之间的平衡中起着核心作用。
Understanding the mechanisms leading to fetal death following maternal subclinical infections is crucial to develop new therapeutic strategies. Here we addressed the relevance of IL-10 secreting B cells (B10) in the maintenance of the immune balance during gestation. mu MT females lacking mature B cells presented normal pregnancies, although their fetuses were smaller and their Treg pool did not expand as in B cell sufficient controls. Pregnant mu MT females were more susceptible to LPS despite having less Treg; their fetuses died at doses compatible with pregnancy in WT animals. Adoptive transfer of IL-10 negative B effector cells or B cells from IL-10 deficient mice did not modify this outcome. The transfer of B10 cells or application of recombinant murine IL-10 reduced the fetal loss, associated with a normalization of Treg numbers and cytokine modulation at the feto-maternal interface. B cell-derived IL-10 suppressed the production of IL-17A and IL-6 by T cells and promoted the conversion of naive cells into Treg. B10 cells are required to restore the immune balance at the feto-maternal interface when perturbed by inflammatory signals. Our data position B cells in a central role in the maintenance of the balance between immunity and tolerance during pregnancy.