IL-26 promotes the pathogenesis of malignant pleural effusion by enhancing CD4(+)IL-22(+) T-cell differentiation and inhibiting CD8(+) T-cell cytotoxicity
IL-26 promotes the pathogenesis of malignant pleural effusion by enhancing CD4(+)IL-22(+) T-cell differentiation and inhibiting CD8(+) T-cell cytotoxicity
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IL-26通过增强CD4( )IL-22( ) T细胞分化和抑制CD8( ) T细胞细胞毒性促进恶性胸腔积液的发病
DOI：
10.1002/jlb.1ma0221-479rr
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发表时间：
2021
影响因子：
5.5
通讯作者：
Zhou Qiong
中科院分区：
文献类型：
--
作者：
Niu Yiran;Ye Linlin;Peng Wenbei;Wang Zihao;Wei Xiaoshan;Wang Xu;Li Yu;Zhang Siyu;Xiang Xuan;Zhou Qiong
IL-26是新近发现的IL-10细胞因子家族成员，主要由Th 17细胞分泌。然而，IL-26与肺癌之间的关系仍不清楚。本研究首次报道IL-26参与恶性胸腔积液（MPE）的产生和促进。检测MPE患者外周血和MPE患者外周血中IL-26和几种Th 17相关细胞因子的浓度。与PB相比，MPE中IL-26、IL-10和IL-6升高。流式细胞仪检测IL-26的细胞来源主要为Th 17细胞，而Tc 17细胞和巨噬细胞也可导致MPE中较高的IL-26浓度。MPE中丰富的IL-6和IL-23可通过磷酸化STAT 3信号通路促进IL-26在CD 4 +T细胞中的表达，进而促进特异性Th 17谱系标志物RORγt的表达。IL-26可通过上调记忆性CD 4 + T细胞分泌IL-22和表达Ki-67，选择性增加Th 22细胞比例。此外，IL-26还能降低颗粒酶B的分泌。与恶性肿瘤细胞共培养时，CD 8 +T细胞的肿瘤杀伤活性也受到抑制。此外，MPE中IL-26蛋白的积累预测患者存活率差。综上所述，我们的结果表明，IL-26通过影响CD 4 +T细胞和CD 8 +T细胞参与MPE的发病机制。
IL-26 is a newly discovered IL-10 cytokine family member mainly secreted by Th17 cells. However, the relationship between IL-26 and lung cancer remains unclear. The present study reported that IL-26 is involved in the production and promotion of malignant pleural effusion (MPE) for the first time. The concentrations of IL-26 and several Th17-related cytokines in MPE and peripheral blood (PB) from MPE patients were measured. IL-26, IL-10, and IL-6 were elevated in MPE compared to PB. The cell resource of IL-26 was primary Th17 cells measured by flow cytometry, whereas Tc17 cells and macrophages could also contribute to higher concentration of IL-26 in MPE. Abundant IL-6 and IL-23 in MPE could promote the frequency of IL-26 expressed by CD4+T cells through phosphorylating STAT3 signaling pathway and promoting the expression of a specific Th17 lineage marker RORγt subsequently. IL-26 could selectively increase Th22 proportion through up-regulating the percentage of Ki-67 expressed by CD4+T cells and the expression of IL-22 secreted by memory CD4+T cells. In addition, IL-26 could decrease secretion of granzyme B. The tumor-killing activity of CD8+T cells were inhibited as well when cocultured with malignant cells. Furthermore, the accumulation of IL-26 protein in MPE predicted poor patient survival. In summary, our results indicated that IL-26 was involved in the pathogenesis of MPE by exerting its impacts on both CD4+T cells and CD8+T cells.