跨膜蛋白 176B (TMEM176B) 主要位于内体膜上，据报道是恶性疾病中的免疫调节因子。然而，该分子在呼吸道病毒感染期间的生物学功能仍未确定。为了研究该基因的功能和预后价值，从基因表达综合数据库中选择了六个基因集进行研究。首先，在不同水平（细胞、外周血、肺组织）评估TMEM176B及其共表达基因的功能。随后，利用机器学习算法分析TMEM176B及其相互作用基因与预后的关系。经过重要性评估和变量筛选后，建立预后模型。最后，通过外部数据集进一步验证了模型的可靠性。进行体外实验来验证TMEM176B的功能。 TMEM176B及其共表达基因参与炎症小体激活、骨髓免疫细胞发育和免疫细胞浸润等多个过程。机器学习进一步筛选了包括 TMEM176B 在内的 27 个相互作用基因模块作为严重呼吸道病毒感染的预后模型，推导集和外部验证集的 ROC 曲线下面积（AUC）分别为 0.986 和 0.905。我们通过体外实验进一步证实，TMEM176B-/- THP-1 分化的巨噬细胞中的病毒载量以及 NLRP3 激活和细胞死亡显着增强。我们的研究表明，TMEM176B 参与呼吸道病毒感染的广泛生物学功能，并具有潜在的预后价值，有望为严重呼吸道病毒感染宿主的临床管理带来新的见解。© 2024 Wiley periodicals LLC。

Transmembrane protein 176B (TMEM176B), localized mainly on the endosomal membrane, has been reported as an immune regulatory factor in malignant diseases. However, the biological function of this molecule remains undetermined during respiratory viral infections. To investigate the functions and prognostic value of this gene, six gene sets were selected from the Gene Expression Omnibus database for research. First, the function of TMEM176B and its co-expressed genes were evaluated at different levels (cell, peripheral blood, lung tissue). Afterwards, a machine learning algorithm was utilized to analyze the relationship between TMEM176B and its interacting genes with prognosis. After importance evaluation and variable screening, a prognostic model was established. Finally, the reliability of the model was further verified through external data sets. In vitro experiments were conducted to validate the function of TMEM176B. TMEM176B and its co-expressed genes are involved in multiple processes such as inflammasome activation, myeloid immune cell development, and immune cell infiltration. Machine learning further screened 27 interacting gene modules including TMEM176B as prognostic models for severe respiratory viral infections, with the area under the ROC curve (AUCs) of 0.986 and 0.905 in derivation and external validation sets, respectively. We further confirmed that viral load as well as NLRP3 activation and cell death were significantly enhanced in TMEM176B-/- THP-1-differentiated macrophages via in vitro experiments. Our study revealed that TMEM176B is involved in a wide range of biological functions in respiratory viral infections and has potential prognostic value, which is expected to bring new insights into the clinical management of severe respiratory viral infection hosts.© 2024 Wiley Periodicals LLC.