白介素-35在结核性胸膜炎发病机制中的作用

Our previous works have demonstrated that regulatory T cells（Tregs） were closely related with autoimmunity of tuberculous patients. Tregs intruded into pleural cavity of tuberculous pleural effusion (TPE), and played local immunosuppressive activity. Interleukin (IL)-35, an immunoregulation effector molecules expressed by Tregs, was supposed to play a very important role in TPE pathogenesis mechanism. This study will extend our previous works and 1) will explore the cell origins of IL-35 in TPE environment; 2) will reveal the dynamics of IL-35 production; 3) will explore regulation and mechanism of IL-35 on generation, differentiation, and chemotactic activity of multiple Th cell subgroups in TPE; 4) will investigate the effects and mechanism of IL-35 in TPE on wound healing and fibrosis of pleural mesothelium; 5) will further evaluate the clinical significance of pleural IL-35 in diagnosis, evaluation of therapeutic efficacy and prognosis of patients with TPE. The accomplishment of this work will elucidate the roles of IL-35 in the pathogenesis of TPE, and will improve differential diagnosis and evaluation of therapeutic efficacy of TPE.

我们的前期研究表明，调节T细胞（Tregs）与结核患者自身免疫密切相关。Tregs浸润到结核性胸膜炎（TPE）患者胸膜腔，并在局部发挥免疫抑制活性。白介素35（IL-35）是Tregs发挥免疫负调控的效应分子，其在TPE中应该具有十分重要的作用。本项目将在此基础上，(1) 探讨在TPE 环境中合成和释放IL-35 的细胞来源；(2)阐明IL-35 的分泌动力学； (3) 探讨TPE 中IL-35 对多种相关T 细胞亚群的发生、分化和趋化活性的影响及其机制； (4)探讨IL-35 在TPE 中胸膜间皮损伤修复和纤维化过程的作用及其机制；(5) 进一步明确IL-35在TPE 诊断和预后评估中的临床价值。本项目的完成将首次阐明IL-35 在TPE 发生机制中的作用，并将有助于改善TPE 的鉴别诊断效率和疗效评估。

我们主要研究了IL-35及IL-12家族其他成员在不同病因胸腔积液患者胸水及血清中的浓度和诊断效能，IL-35对胸膜间皮细胞的短期和长期增殖修复的影响，应用流式细胞仪检测结核性胸膜炎患者胸水和血清IL-35的浓度以及细胞来源。发现IL-12、IL-27、IL-35在结核性胸腔积液中较恶性胸腔积液中表达均升高，可能共同参与了结核性胸腔积液胸膜腔炎症的发生，并对结核性胸腔积液有一定的诊断意义。