一种新兴的IL-10家族细胞因子—白介素-26在结核性胸膜炎发病机制中的作用

我们既往研究证实了多种CD4+T细胞和细胞因子在结核性胸膜炎(TPE)发生发展中的免疫调节作用。作为IL-10家族成员，白介素(IL)-26在结核感染免疫中的研究显著滞后。仅有的一项研究初步提示IL-26有利于结核杆菌的存活，但此结论与已广泛报道的IL-26的“杀菌”活性相悖。我们前期检测到TPE中的IL-26水平显著高于外周血，CD4+T细胞是其主要来源，其中Th1和Th17细胞均分泌IL-26并表达其受体。采用ESAT6/CFP10刺激TPE的单个核细胞显著增加IL-26+细胞数量及其受体的表达。上述结论表明IL-26参与结核免疫反应并与CD4+T细胞存在相互作用。本项目拟明确IL-26在TPE中的免疫学活性、与其它IL-10家族因子间的相互调节、对CD4+T细胞及胸膜间皮细胞增殖、分化和生物学行为的影响，以此阐明IL-26在TPE发生机制中的作用，并评估其在诊断和预后中的临床价值。

Our previous works have provided that CD4+T lymphocytes and some cytokines are critical for the immunoregulation and development of tuberculous pleural effusion (TPE). The interleukin (IL)-10 family of cytokines has diverse roles during Mycobacterium tuberculosis (Mtb) infection ranging from immune evasion to immune protection. However, the roles of IL-26, an emerging member of the IL-10 family, in the regulation of host defense against Mtb remain poorly understood. There is only one study demonstrated the possible role of IL-26 in Mtb infection. The addition of recombinant IL-26 to whole blood infected with Mtb led to enhanced bacterial survival and growth, which is in contrast with the widely reported “microbicidal” functions of IL-26. In order to deeply explore the immunoregulation of IL-26 in TPE, we demonstrated that IL-26 was significantly higher in TPE than in blood, and the most IL-26-producing T cells were CD4+ T cells. Th1 and Th17 cells produced IL-26 and expressed IL-20R1 (receptor of IL-26). The addition of tuberculosis-specific antigen ESAT6/CFP10 to the mononuclear cells isolated from TPE led to increasing the number of IL-26-producing cell and its receptor. Our data suggest a collaborative loop between IL-26 and CD4+ T cells in pathogenesis of TPE. This study will extend our previous works and 1) will explore the cell origins and dynamics of IL-26 in TPE environment; 2) will explore the interaction regulation with IL-26 and other IL-10 family members in TPE; 3) will investigate the regulation and mechanism of IL-26 on generation, differentiation, and chemotactic activity of multiple CD4+ T cell subgroups in TPE; 4)will explore the effects and mechanism of IL-26 in TPE on biological characteristics and fibrosis of pleural mesothelium; 5) will further evaluate the clinical significance of pleural IL-26 in pathological changes, diagnosis, evaluation of therapeutic efficacy and prognosis of patients with TPE. The accomplishment of this work will elucidate the immunological activity of IL-26 in the pathogenesis of TPE, and will improve differential diagnosis and evaluation of therapeutic efficacy of TPE.