Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Am J Reprod Immunol. 2021 Sep;86(3):e13380. doi: 10.1111/aji.13380. Epub 2021 Jul 20.
Inflammation and immune responses play crucial roles in the development of endometriosis. Although interleukin-9 (IL-9) has a pro-inflammatory function in chronic inflammatory diseases, its function in endometriosis remains unknown. Here, we aimed to investigate the significance of IL-9 and IL-9-producing lymphocytes in endometriosis.
Specimens were obtained from patients with and without endometriosis. Peritoneal fluid (PF), peripheral blood (PB), and ovarian endometrioma (OE) tissues were analyzed for the proportion of CD4 IL-9 lymphocytes and IL-9 concentration using flow cytometry and enzyme-linked immunosorbent assay. OE, endometrium with endometriosis (EE), and normal endometrium (NE) were analyzed for IL-9 receptor (IL-9R) expression using immunohistochemical staining. IL-9-dependent changes in Interleukin-8 (IL-8) expression in endometrial stromal cells from OE (OESCs) were evaluated using real-time PCR.
The proportion of CD4 IL-9 lymphocytes was higher in the PF, but not the PB, of patients with endometriosis than individuals without endometriosis (p < .05). However, IL-9 levels in the PF did not differ between those with and without endometriosis. We detected CD4+ IL-9+ lymphocytes in OE tissues and IL-9R in OE tissues and OESCs. In OESC culture, IL-9 significantly elevated IL-8 expression in a dose-dependent manner (p < .05), which was nullified by the addition of the anti-IL-9 receptor antibody. Furthermore, IL-9 additively stimulated IL-8 expression in the presence of TNF-α (p < .05).
Our findings show that IL-9 produced by helper T cells induces IL-8 expression, suggesting that IL-9 plays an important role in the development of endometriosis by stimulating IL-8 expression.
炎症和免疫反应在子宫内膜异位症的发展中起着至关重要的作用。虽然白细胞介素-9（IL-9）在慢性炎症性疾病中有促炎作用，但它在子宫内膜异位症中的作用尚不清楚。在这里，我们旨在研究 IL-9 和产生 IL-9 的淋巴细胞在子宫内膜异位症中的意义。
获取患有和不患有子宫内膜异位症的患者的标本。使用流式细胞术和酶联免疫吸附试验分析腹膜液（PF）、外周血（PB）和卵巢子宫内膜异位症（OE）组织中 CD4 IL-9 淋巴细胞的比例和 IL-9 浓度。使用免疫组织化学染色分析 OE、有子宫内膜异位症的子宫内膜（EE）和正常子宫内膜（NE）中的 IL-9 受体（IL-9R）表达。使用实时 PCR 评估 OE 中的子宫内膜基质细胞（OESCs）中 IL-9 依赖性白细胞介素-8（IL-8）表达的变化。
与无子宫内膜异位症的个体相比，子宫内膜异位症患者的 PF 中 CD4 IL-9 淋巴细胞的比例较高，但 PB 中无差异（p <.05）。然而，PF 中的 IL-9 水平在有和无子宫内膜异位症的患者之间没有差异。我们在 OE 组织中检测到 CD4+ IL-9+ 淋巴细胞和 OE 组织和 OESCs 中的 IL-9R。在 OESC 培养中，IL-9 以剂量依赖性方式显著升高 IL-8 表达（p <.05），添加抗 IL-9 受体抗体可使其无效。此外，在存在 TNF-α 的情况下，IL-9 可协同刺激 IL-8 表达（p <.05）。
我们的研究结果表明，辅助性 T 细胞产生的 IL-9 诱导 IL-8 表达，表明 IL-9 通过刺激 IL-8 表达在子宫内膜异位症的发展中起重要作用。
