Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, PR China.
PLoS One. 2012;7(10):e48566. doi: 10.1371/journal.pone.0048566. Epub 2012 Oct 30.
It has been shown that IL-9 plays a proinflammatory role in the pathogenesis of certain autoimmune diseases. This study was designed to investigate the possible role of IL-9 in the development of experimental autoimmune uveoretinitis (EAU) and the effect of IFN-β on its expression.
EAU was induced in B10RIII mice by immunization with interphotoreceptor retinoid-binding protein peptide 161-180 (IRBP(161-180)). IFN-β was administered subcutaneously to IRBP(161-180) immunized mice every other day from day one before immunization to the end of the study. Splenocytes and draining lymph node (DLN) cells from EAU mice or control mice or EAU mice treated with IFN-β or PBS were stimulated with anti-CD3/CD28 or IRBP(161-180) for 3 days. Naïve T cells cultured under Th1 or Th17 polarizing conditions were incubated in the presence or absence of IFN-β for 4 days. Effector/memory T cells were activated by anti-CD3/CD28 in the presence or absence of IFN-β for 3 days. IFN-β-treated monocytes were cocultured with naïve T cells or effector/memory T cells for 3 days. Culture supernatants were collected and IL-9 was detected by ELISA.
IL-9 expression in splenocytes and DLN cells was increased in EAU mice during the inflammatory phase and returned back to lower levels during the recovery phase. IFN-β in vivo treatment significantly inhibited EAU activity in association with a down-regulated expression of IL-9. In vitro polarized Th1 and Th17 cells both secreted IL-9 and the addition of IFN-β suppressed production of IL-9 by both Th subsets. Beside its effect on polarized Th cells, IFN-β also suppressed the secretion of IL-9 by effector/memory T cells. However, IFN-β-treated monocytes had no effect on the production of IL-9 when cocultured with naïve or effector/memory T cells.
IL-9 expression is increased during EAU which could be suppressed by IFN-β.
已经证明白细胞介素 9（IL-9）在某些自身免疫性疾病的发病机制中发挥促炎作用。本研究旨在探讨 IL-9 在实验性自身免疫性葡萄膜炎（EAU）发展中的可能作用，以及 IFN-β 对其表达的影响。
通过用 161-180 个视黄醛结合蛋白肽（IRBP（161-180））免疫 B10RIII 小鼠来诱导 EAU。从免疫前一天开始，每隔一天给 IRBP（161-180）免疫的小鼠皮下注射 IFN-β，直到研究结束。从 EAU 小鼠或对照小鼠或用 IFN-β 或 PBS 治疗的 EAU 小鼠的脾细胞和引流淋巴结（DLN）细胞中刺激抗 CD3/CD28 或 IRBP（161-180）3 天。在 Th1 或 Th17 极化条件下培养的幼稚 T 细胞在存在或不存在 IFN-β的情况下孵育 4 天。在存在或不存在 IFN-β的情况下，用抗 CD3/CD28 激活效应/记忆 T 细胞 3 天。用 IFN-β 处理的单核细胞与幼稚 T 细胞或效应/记忆 T 细胞共培养 3 天。收集培养上清液，通过 ELISA 检测 IL-9。
在炎症期，EAU 小鼠的脾细胞和 DLN 细胞中 IL-9 的表达增加，在恢复期恢复到较低水平。体内 IFN-β 治疗显著抑制 EAU 活性，同时下调 IL-9 的表达。体外极化的 Th1 和 Th17 细胞均分泌 IL-9，IFN-β 的添加抑制了这两个 Th 亚群产生 IL-9。除了对极化 Th 细胞的作用外，IFN-β 还抑制了效应/记忆 T 细胞分泌 IL-9。然而，IFN-β 处理的单核细胞与幼稚或效应/记忆 T 细胞共培养时，对 IL-9 的产生没有影响。
IL-9 在 EAU 期间表达增加，可被 IFN-β 抑制。
