探讨转化生长因子-β活化激酶1结合蛋白1(TGF-β activated kinase-1-binding protein 1, TAB1)对免疫麻痹相关表型的调控作用，为重症肺炎预后判断提供潜在标志物。

基于GSE65682数据集，纳入183例重症肺炎患者为观察组及42例健康者为对照组，分析TAB1表达差异；采用单因素Cox比例风险回归模型判断TAB1表达与患者预后关联。以人单核细胞来源巨噬细胞(human monocyte-derived macrophages, MDMs)为模型，通过RNA干扰敲低TAB1，分别采用流式细胞术、蛋白质印迹法(Western blot)和实时荧光定量聚合酶链式反应(polymerase chain reaction, PCR)检测吞噬能力、人类白细胞抗原DR(human leukocyte antigen DR, HLA-DR)表达、巨噬细胞极化及促炎因子基因转录水平的变化。

①健康对照者外周血TAB1表达水平显著高于重症肺炎患者(P<0.05)，存活患者表达水平显著高于死亡患者(P<0.01)；单因素Cox回归分析显示，TAB1高表达与良好预后显著相关(HR＝0.029，95%CI：0.004~0.214，P<0.001)；②与对照组相比，si-TAB1组MDMs吞噬率降低(56.2%比16.8%)(P<0.001)，M2型巨噬细胞(CD80^－ CD206^＋)比例升高(7.33%比32.4%)(P<0.05)，HLA-DR蛋白表达显著降低(P<0.001)；促炎因子白细胞介素-1β(Interleukin-1 beta, IL-1β)、IL6和肿瘤坏死因子(tumor necrosis factor, TNF)的mRNA相对表达水平显著下调(P<0.01)。

TAB1高表达与重症肺炎良好预后相关，敲低TAB1可诱导MDMs呈现吞噬功能缺陷、HLA-DR低表达、M2型偏移及促炎因子抑制等典型免疫麻痹表型，TAB1有望成为重症肺炎预后及免疫状态监测的潜在分子标志物。

To investigate the regulatory effect of TGF-β activated kinase-1-binding protein 1 (TAB1) on immunoparalysisrelated phenotypes and to provide a potential biomarker for prognosis assessment in severe pneumonia.

Based on the GSE65682 dataset, 183 patients with severe pneumonia and 42 healthy controls were enrolled, and the differential expression of TAB1 was analyzed. Univariate Cox proportional hazards regression model was used to evaluate the association between TAB1 expression and patient prognosis. Human monocytederived macrophages (MDMs) were used as a model, and TAB1 was knocked down by RNA interference. Flow cytometry, Western blot, and realtime quantitative polymerase chain reaction (PCR) were employed to detect phagocytic capacity, human leukocyte antigen DR (HLADR) expression, macrophage polarization, and changes in the transcriptional levels of proinflammatory cytokine genes.

(1) The expression level of TAB1 in peripheral blood was significantly higher in healthy controls than in patients with severe pneumonia (P<0.05), and significantly higher in survivors than in nonsurvivors (P<0.01). Univariate Cox regression analysis showed that high TAB1 expression was significantly associated with favorable prognosis (HR=0.029, 95%CI: 0.004~0.214, P<0.001). (2) Compared with the control group, the siTAB1 group exhibited a decreased phagocytosis rate (56.2% vs. 16.8%, P<0.001), an increased proportion of M2 macrophages (CD80^- CD206⁺ ) (7.33% vs. 32.4%, P<0.05), and significantly reduced HLADR protein expression (P<0.001). The mRNA relative expression levels of proinflammatory cytokines interleukin1β (IL1β), IL6, and tumor necrosis factor (TNF) were significantly downregulated (P<0.01).

High TAB1 expression is associated with favorable prognosis in severe pneumonia. Knockdown of TAB1 induces typical immunoparalysis phenotypes in MDMs, including phagocytic dysfunction, low HLADR expression, M2 polarization, and suppression of proinflammatory cytokines. TAB1 holds promise as a potential molecular biomarker for prognosis and immune status monitoring in severe pneumonia.