Functional expression of aryl hydrocarbon receptor on mast cells populating human endometriotic tissues.
Functional expression of aryl hydrocarbon receptor on mast cells populating human endometriotic tissues.
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DOI：
10.1038/labinvest.2016.74
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发表时间：
2016-09
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影响因子：
--
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子宫内膜异位症是一种炎症性疾病，其特征是子宫外存在异位的子宫内膜组织。肥大细胞（MC）的弥漫性浸润在整个子宫内膜异位症病变中观察到，但很少有人知道这些细胞如何有助于调节异位子宫内膜种植体的生长和促进子宫内膜异位症相关炎症的分子网络。芳烃受体（Aryl Hydrocarbon Receptor，AhR）是一种对环境毒素和内源性化合物产生应答的转录因子，存在于MCs中。响应于AhR激活，MC产生IL-17和活性氧，突出了AhR配体通过MC对炎症的潜在影响。在这里，我们研究了子宫内膜MCs通过感受AhR配体促进炎症微环境，从而维持子宫内膜异位症发展的可能性。使用人增生组织（ET）样品，我们进行了以下实验：i）检查细胞因子表达谱; ii）计数表达AhR的MC; iii）验证表达AhR的MC的表型以确定MC是否具有致耐受性。（IL-10阳性）或炎症（IL-17阳性）表型; iv）测量AhR配体的存在（犬尿氨酸衍生物）和犬尿氨酸代谢酶（吲哚胺2，3-双加氧酶1（IDO 1））; v）在体外用AhR拮抗剂处理ET器官培养物以测量细胞因子环境的变化;和vi）测量用AhR活化的MC条件培养基培养的子宫内膜基质细胞的生长。我们发现，ET组织有利于细胞因子的产生，协调慢性炎症和表达AhR的MC的IL-17和IL-10阳性的群体。与对照组织相比，ET富含IDO 1和AhR配体犬尿氨酸，可能通过AhR促进MC活化。ET对AhR拮抗剂治疗敏感，在AhR激活后MCs释放的可溶性因子存在下，子宫内膜基质细胞生长得到改善。这些结果提示MCs在子宫内膜异位症发病机制中的新机制作用。
Endometriosis is an inflammatory disease characterized by the presence of ectopic endometrial tissue outside the uterus. A diffuse infiltration of mast cells (MCs) is observed throughout endometriotic lesions, but little is known about how these cells contribute to the network of molecules that modulate the growth of ectopic endometrial implants and promote endometriosis-associated inflammation. The Aryl Hydrocarbon Receptor (AhR), a transcription factor known to respond to environmental toxins and endogenous compounds, is present in MCs. In response to AhR activation, MCs produce IL-17 and reactive oxygen species, highlighting the potential impact of AhR ligands on inflammation via MCs. Here, we investigated the possibility that endometrial MCs promote an inflammatory microenvironment by sensing AhR ligands, thus sustaining endometriosis development. Using human endometriotic tissue (ET) samples, we performed the following experiments: i) examined the cytokine expression profile; ii) counted AhR-expressing MCs; iii) verified the phenotype of AhR-expressing MCs to establish whether MCs have a tolerogenic (IL-10-positive) or inflammatory (IL-17-positive) phenotype; iv) measured the presence of AhR ligands (tryptophan-derived kynurenine) and tryptophan-metabolizing enzymes (indoleamine 2,3-dioxygenase 1 (IDO1)); v) treated ET organ cultures with an AhR antagonist in vitro to measure changes in the cytokine milieu; and vi) measured the growth of endometrial stromal cells cultured with AhR-activated MC-conditioned medium. We found that ET tissue was conducive to cytokine production, orchestrating chronic inflammation and a population of AhR-expressing MCs that are both IL-17 and IL-10-positive. ET was rich in IDO1 and the AhR-ligand kynurenine compared with control tissue, possibly promoting MC activation through AhR. ET was susceptible to treatment with an AhR antagonist, and endometrial stromal cell growth was improved in the presence of soluble factors released by MCs upon AhR activation. These results suggest a new mechanistic role of MCs in the pathogenesis of endometriosis.
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影响因子：
3.7
作者：
Domenis R;Bergamin N;Gianfranceschi G;Vascotto C;Romanello M;Rigo S;Vagnarelli G;Faggiani M;Parodi P;Kelley MR;Beltrami CA;Cesselli D;Tell G;Beltrami AP
通讯作者：
Beltrami AP
影响因子：
5.8
作者：
Hernandez-Ochoa, Isabel;Karman, Bethany N.;Flaws, Jodi A.
通讯作者：
Flaws, Jodi A.
影响因子：
20.3
作者：
Beltrami, Antonio R.;Cesselli, Daniela;Beltrami, Carlo A.
通讯作者：
Beltrami, Carlo A.
DOI：
10.1016/j.ijgo.2010.03.039
发表时间：
2010-09-01
影响因子：
3.8
作者：
Ferrero, Simone;Arena, Elisa;Remorgida, Valentino
通讯作者：
Remorgida, Valentino
影响因子：
2.1
作者：
Laufer, Marc R.
通讯作者：
Laufer, Marc R.