Sex Hormones and Aging Modulate Interferon Lambda 1 Production and Signaling by Human Uterine Epithelial Cells and Fibroblasts.
Sex Hormones and Aging Modulate Interferon Lambda 1 Production and Signaling by Human Uterine Epithelial Cells and Fibroblasts.
复制标题
DOI：
10.3389/fimmu.2021.718380
复制
发表时间：
2021
影响因子：
7.3
通讯作者：
Wira CR
中科院分区：
文献类型：
--
作者：
Patel MV;Hopkins DC;Barr FD;Wira CR
雌二醇（E2）和孕酮（P）对人类子宫内膜的免疫功能具有强效作用，这对于创造有利于成功生殖的环境至关重要。III型/λ（λ）干扰素（IFN）涉及胎盘对病毒病原体的免疫防御，其在高E2和P水平的背景下发生。然而，E2和P在调节非妊娠人子宫内膜中IFNλ1的表达和功能中的作用尚不清楚。我们产生纯化的人子宫上皮细胞和基质成纤维细胞从子宫切除标本回收的体外培养。Poly（I：C）是一种病毒dsRNA模拟物，可有效增加上皮细胞和成纤维细胞分泌IFNλ1。poly（I：C）刺激后，上皮细胞分泌的IFNλ1随着年龄的增长而显着增加。用E2（5 × 10 - 8 M）或P（1 × 10 - 7 M）刺激任一细胞类型，单独或在poly（I：C）存在下对IFNλ1的表达或分泌均无影响。E2抑制IFNλ1诱导的上皮细胞抗病毒IFN刺激基因（ISG）MxA、OAS 2和ISG 15的上调，但不抑制成纤维细胞。用雷洛昔芬阻断雌激素受体α（ERα）表明，E2通过ERα介导其对ISG表达的抑制作用。与E2相反，P增强了IFNλ1对ISG 15的上调，但对上皮细胞中的MxA和OAS 2没有影响。我们的结果表明，E2和P对IFNλ1诱导的ISGs的作用具有细胞类型特异性。E2介导的抑制和选择性P介导的刺激IFNλ1诱导的子宫上皮细胞ISG表达表明IFNλ1的作用随月经周期阶段、妊娠和绝经状态而变化。E2的抑制作用可能是下生殖道上行病原体感染妊娠和非妊娠子宫内膜的潜在机制。
Estradiol (E2) and progesterone (P) have potent effects on immune function in the human uterine endometrium which is essential for creating an environment conducive for successful reproduction. Type III/lambda (λ) interferons (IFN) are implicated in immune defense of the placenta against viral pathogens, which occurs against the backdrop of high E2 and P levels. However, the effect of E2 and P in modulating the expression and function of IFNλ1 in the non-pregnant human uterine endometrium is unknown. We generated purified in vitro cultures of human uterine epithelial cells and stromal fibroblast cells recovered from hysterectomy specimens. Poly (I:C), a viral dsRNA mimic, potently increased secretion of IFNλ1 by both epithelial cells and fibroblasts. The secretion of IFNλ1 by epithelial cells significantly increased with increasing age following poly (I:C) stimulation. Stimulation of either cell type with E2 (5x10-8M) or P (1x10-7M) had no effect on expression or secretion of IFNλ1 either alone or in the presence of poly (I:C). E2 suppressed the IFNλ1-induced upregulation of the antiviral IFN-stimulated genes (ISGs) MxA, OAS2 and ISG15 in epithelial cells, but not fibroblasts. Estrogen receptor alpha (ERα) blockade using Raloxifene indicated that E2 mediated its inhibitory effects on ISG expression via ERα. In contrast to E2, P potentiated the upregulation of ISG15 in response to IFNλ1 but had no effect on MxA and OAS2 in epithelial cells. Our results demonstrate that the effects of E2 and P on IFNλ1-induced ISGs are cell-type specific. E2-mediated suppression, and selective P-mediated stimulation, of IFNλ1-induced ISG expression in uterine epithelial cells suggest that the effects of IFNλ1 varies with menstrual cycle stage, pregnancy, and menopausal status. The suppressive effect of E2 could be a potential mechanism by which ascending pathogens from the lower reproductive tract can infect the pregnant and non-pregnant endometrium.
登录
查看更多内容
影响因子：
5.8
作者：
BAIRD, DT;FRASER, IS
通讯作者：
FRASER, IS
影响因子：
5.8
作者：
Huhtinen, Kaisa;Desai, Reena;Poutanen, Matti
通讯作者：
Poutanen, Matti
影响因子：
4.8
作者：
Joyce, MM;White, FJ;Johnson, GA
通讯作者：
Johnson, GA
影响因子：
4
作者：
Hillyer, Philippa;Mane, Viraj P.;Schramm, Lynnsie M.;Puig, Montserrat;Verthelyi, Daniela;Chen, Aaron;Zhao, Zeng;Navarro, Maria B.;Kirschman, Kevin D.;Bykadi, Srikant;Jubin, Ronald G.;Rabin, Ronald L.
通讯作者：
Rabin, Ronald L.
影响因子：
6.4
作者：
Ghosh, Mimi;Shen, Zheng;Wira, Charles R.
通讯作者：
Wira, Charles R.