Interleukin‐9 produced by helper T cells stimulates interleukin‐8 expression in endometriosis
Interleukin‐9 produced by helper T cells stimulates interleukin‐8 expression in endometriosis
复制标题
辅助 T 细胞产生的白细胞介素 9 刺激子宫内膜异位症中白细胞介素 8 的表达
DOI：
10.1111/aji.13380
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发表时间：
2020
影响因子：
3.6
通讯作者：
Kitawaki Jo
中科院分区：
文献类型：
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作者：
Tarumi Yosuke;Mori Taisuke;Okimura Hiroyuki;Maeda Eiko;Tanaka Yukiko;Kataoka Hisashi;Ito Fumitake;Koshiba Akemi;Kusuki Izumi;Kitawaki Jo
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具有促炎作用，但其在子宫内膜异位症中的作用尚不清楚。本研究旨在探讨IL-9和IL-9产生淋巴细胞在子宫内膜异位症中的意义。研究方法标本取自子宫内膜异位症患者和非子宫内膜异位症患者。采用流式细胞术和酶联免疫吸附试验分析了腹膜液（PF）、外周血（PB）和卵巢恶性肿瘤（OE）组织中CD 4 +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、子宫内膜异位症（EE）和正常子宫内膜（NE）的IL-9受体（IL-9 R）表达。采用真实的时间PCR.ResultsThe比例的CD 4 +IL-9+淋巴细胞的PF，但不是PB，子宫内膜异位症患者比个人没有子宫内膜异位症（p<0.05）的OE（OESCs）的子宫内膜基质细胞中白细胞介素8（IL-8）表达的IL-9依赖性变化进行了评估。然而，PF中的IL-9水平在有和没有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CD 4 + IL-9+淋巴细胞，在OE组织和OESC中检测到IL-9 R。在OESC培养物中，IL-9以剂量依赖性方式显著升高IL-8表达（p<0.05），加入抗IL-9受体抗体可使其无效。此外，IL-9在TNF-α存在下额外刺激IL-8的表达（p< .05）。结论我们的研究结果表明，辅助性T细胞产生的IL-9诱导IL-8的表达，这表明IL-9通过刺激IL-8的表达在子宫内膜异位症的发展中起着重要作用。
ProblemInflammation 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.Method of studySpecimens 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.ResultsThe 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).ConclusionOur 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.