Interleukin-33-induced expression of PIBF1 by decidual B cells protects against preterm labor.

Interleukin-33-induced expression of PIBF1 by decidual B cells protects against preterm labor.
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DOI:
10.1038/nm.4244
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发表时间:
2017-01
期刊:
影响因子:
82.9
通讯作者:
Chen K
Chen K
中科院分区:
医学1区
文献类型:
--
作者:
Huang B;Faucette AN;Pawlitz MD;Pei B;Goyert JW;Zhou JZ;El-Hage NG;Deng J;Lin J;Yao F;Dewar RS 3rd;Jassal JS;Sandberg ML;Dai J;Cols M;Shen C;Polin LA;Nichols RA;Jones TB;Bluth MH;Puder KS;Gonik B;Nayak NR;Puscheck E;Wei WZ;Cerutti A;Colonna M;Chen K

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早产(PTB)是全世界新生儿死亡的主要原因。宫内和全身感染和炎症导致 30-40% 的自发性早产 (PTL),先于 PTB。尽管抗体产生是针对感染的主要免疫防御机制,并且 B 细胞功能障碍与 PTL 相关的妊娠并发症有关,但 B 细胞在妊娠中的功能尚不清楚。我们发现接受自发性 PTL 的女性的绒毛蜕膜含有功能改变的 B 细胞群。炎症后,B 细胞缺陷小鼠明显比野生型 (WT) 小鼠更容易受到 PTL 的影响,但 B 细胞赋予白细胞介素 (IL)-10 独立的针对 PTL 的保护作用。小鼠 B 细胞缺陷导致子宫活性孕酮诱导的阻断因子 1 (PIBF1) 水平降低,而 PIBF1 的治疗性给药可减轻 B 细胞缺陷小鼠的 PTL 和子宫炎症。 B 细胞是妊娠晚期人类绒毛膜蜕膜和小鼠子宫中 PIBF1 的重要产生者。 B 细胞的 PIBF1 表达是由粘膜报警蛋白 IL-33 诱导的(参考文献)。人 PTL 与绒毛膜蜕膜 B 细胞上 IL-33 受体 a 链表达减少以及妊娠晚期绒毛蜕膜中活性 PIBF1 水平较低有关。这些结果定义了涉及 IL-33、蜕膜 B 细胞和 PIBF1 在保障足月妊娠中的重要调控级联,并提出了基于 IL-33 和 PIBF1 的新治疗方法来预防人类 PTL。
Preterm birth (PTB) is a leading cause of neonatal death worldwide. Intrauterine and systemic infection and inflammation cause 30–40% of spontaneous preterm labor (PTL), which precedes PTB. Although antibody production is a major immune defense mechanism against infection, and B cell dysfunction has been implicated in pregnancy complications associated with PTL, the functions of B cells in pregnancy are not well known. We found that choriodecidua of women undergoing spontaneous PTL harbored functionally altered B cell populations. B cell–deficient mice were markedly more susceptible than wild-type (WT) mice to PTL after inflammation, but B cells conferred interleukin (IL)-10-independent protection against PTL. B cell deficiency in mice resulted in a lower uterine level of active progesterone-induced blocking factor 1 (PIBF1), and therapeutic administration of PIBF1 mitigated PTL and uterine inflammation in B cell–deficient mice. B cells are a significant producer of PIBF1 in human choriodecidua and mouse uterus in late gestation. PIBF1 expression by B cells is induced by the mucosal alarmin IL-33 (ref.). Human PTL was associated with diminished expression of the a-chain of IL-33 receptor on choriodecidual B cells and a lower level of active PIBF1 in late gestation choriodecidua. These results define a vital regulatory cascade involving IL-33, decidual B cells and PIBF1 in safeguarding term pregnancy and suggest new therapeutic approaches based on IL-33 and PIBF1 to prevent human PTL.
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