白细胞介素-26在炎症性肠病中的表达及其对巨噬细胞的免疫调节作用。
Interleukin-26 Expression in Inflammatory Bowel Disease and Its Immunoregulatory Effects on Macrophages.
作者信息
Song Dongjuan, Lai Lijie, Lu Juntao, Tong Jinlu, Ran Zhihua
机构信息
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
出版信息
Front Med (Lausanne). 2022 Apr 6;9:797135. doi: 10.3389/fmed.2022.797135. eCollection 2022.
BACKGROUND AND AIM
Interleukin-26 (IL-26) has been implicated in several chronic inflammatory diseases. However, its role in inflammatory bowel disease (IBD) remains to be elucidated. We aimed to investigate IL-26 expression in IBD and its immunoregulatory effects on macrophages.
METHODS
We assessed IL-26 expression in the intestinal mucosa and blood samples of IBD patients and healthy controls (HC). The associations between the clinical characteristics of IBD and IL-26 expression levels in serum and peripheral blood mononuclear cells (PBMCs) were investigated. In addition, the transcriptional changes in THP-1 macrophages exposed to IL-26 were determined by RNA sequencing and validated with qRT-PCR, ELISA and western blots.
RESULTS
Compared with HC, in IBD patients, IL-26 expression levels were elevated in the inflamed intestinal mucosa, and reduced in serum and PBMCs. IL-26 mRNA levels in PBMCs, but not serum IL-26 levels, were inversely correlated with disease activity in IBD. Furthermore, IL-26 mRNA levels in PBMCs were significantly lower in patients with complicated Crohn's disease. A total of 1,303 differentially expressed protein-coding genes were identified between untreated and IL-26-treated macrophages. The up-regulated genes showed enrichment in some inflammatory and immune-related processes and pathways. Additionally, GSEA showed that neutrophil, monocyte, and lymphocyte chemotaxis was significantly enriched in IL-26-treated macrophages. Further validation revealed that IL-26 promotes the secretion of multiple inflammatory cytokines and chemokines and upregulates the expression of adhesion molecules, MMP-8, and MMP-9 while inhibiting MMP-1 in macrophages.
CONCLUSION
Compared with HC, in IBD patients, IL-26 levels were elevated in the inflamed intestinal mucosa, and reduced in the peripheral blood. The transcriptional changes in macrophages exposed to IL-26 suggest that IL-26 may amplify the aberrant immune response in IBD by activating macrophages.
背景与目的
白细胞介素-26（IL-26）与多种慢性炎症性疾病有关。然而，其在炎症性肠病（IBD）中的作用仍有待阐明。我们旨在研究IL-26在IBD中的表达及其对巨噬细胞的免疫调节作用。
方法
我们评估了IBD患者和健康对照（HC）的肠黏膜和血液样本中IL-26的表达。研究了IBD的临床特征与血清和外周血单个核细胞（PBMC）中IL-26表达水平之间的关联。此外，通过RNA测序确定暴露于IL-26的THP-1巨噬细胞中的转录变化，并用qRT-PCR、ELISA和western印迹进行验证。
结果
与HC相比，IBD患者炎症肠黏膜中IL-26表达水平升高，而血清和PBMC中IL-26表达水平降低。PBMC中的IL-26 mRNA水平而非血清IL-26水平与IBD的疾病活动呈负相关。此外，复杂性克罗恩病患者PBMC中的IL-26 mRNA水平显著降低。在未处理和IL-26处理的巨噬细胞之间共鉴定出1303个差异表达的蛋白质编码基因。上调的基因在一些炎症和免疫相关过程及途径中显示出富集。此外，基因集富集分析（GSEA）表明，IL-26处理的巨噬细胞中中性粒细胞、单核细胞和淋巴细胞趋化性显著富集。进一步验证表明，IL-26促进巨噬细胞分泌多种炎性细胞因子和趋化因子，并上调黏附分子、MMP-8和MMP-9的表达，同时抑制巨噬细胞中的MMP-1。
结论
与HC相比，IBD患者炎症肠黏膜中IL-26水平升高，外周血中IL-26水平降低。暴露于IL-26的巨噬细胞中的转录变化表明，IL-26可能通过激活巨噬细胞放大IBD中的异常免疫反应。
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