辅助 T (Th) 9 细胞是 Th 细胞的一个新亚群，独立于 Th2 细胞发育，其特点是分泌白细胞介素 (IL)-9。研究表明，Th9细胞参与多种疾病，如过敏性疾病和肺部疾病（例如哮喘、慢性阻塞性气道疾病、慢性鼻窦炎、鼻息肉和肺发育不全）、代谢性疾病（例如急性白血病、粒细胞白血病、乳腺癌）。癌症、肺癌、黑色素瘤、胰腺癌）、神经精神疾病（例如阿尔茨海默病）、自身免疫性疾病（例如格雷夫斯病、克罗恩病、结肠炎、牛皮癣、系统性红斑狼疮、系统性硬皮病、类风湿性关节炎、多发性硬化症、炎症性肠病）病、特应性皮炎、湿疹）和传染病（例如结核病、肝炎）。然而，关于其参与其他代谢、神经精神和传染病的信息还很缺乏。本研究旨在从公开的基因中识别 Th2 细胞向 Th9 细胞转化过程中显着差异改变的基因，以及它们的调节 microRNA (miR)小鼠模型的表达综合数据集，使用计算机分析来阐明疾病过程中涉及的各种致病途径。使用从 2 个公开可用的数据集（GSE99166 和 GSE123501）中识别出的差异表达基因 (DEG)，我们进行了功能富集和网络分析来识别通路、蛋白质-蛋白质相互作用、miR-信使 RNA 关联以及与 Th2 细胞向 Th9 细胞转化中涉及的显着差异改变基因相关的疾病-基因关联。我们从数据集 GSE99166 和 GSE123501 的表达谱。共差异表达的 IL、细胞因子、受体和转录因子 (TF) 在 7 个关键的京都基因和基因组途径百科全书以及基因本体中得到丰富。我们构建了蛋白质-蛋白质相互作用网络并预测了参与 Th2 至 Th9 分化途径的顶级调控 miR。我们还确定了各种代谢性疾病、过敏性疾病、肺病、神经精神疾病、自身免疫性疾病和传染病以及癌症，其中 Th2 向 Th9 的分化可能发挥着至关重要的作用。这项研究确定了 Th9 与疾病状态之间迄今为止尚未探索的可能关联。一些重要的IL，包括CCL1（趋化因子[C-C基序]配体1）、CCL20（趋化因子[C-C基序]配体20）、IL-13、IL-4、IL-12A和IL-9；受体，包括 IL-12RB1、IL-4RA（白细胞介素 9 受体 α）、CD53（分化簇 53）、CD6（分化簇 6）、CD5（分化簇 5）、CD83（分化簇 83）、CD197 （分化簇 197）、IL-1RL1（白细胞介素 1 受体样 1）、CD101（分化簇 101）、CD96（分化簇 96）、CD72（分化簇 72）、CD7（分化簇 7） 、CD152（细胞毒性 T 淋巴细胞相关蛋白 4）、CD38（分化簇 38）、CX3CR1（趋化因子 [C-X3-C 基序]受体 1）、CTLA2A（细胞毒性 T 淋巴细胞相关蛋白 2 α）、CTLA28 和CD196（分化簇196）；和转录因子，包括 FOXP3（叉头盒 P3）、IRF8（干扰素调节因子 8）、FOXP2（叉头盒 P2）、RORA（RAR 相关孤儿受体 α）、AHR（芳基烃受体）、MAF（禽类肌肉腱膜纤维肉瘤癌基因）同源物）、SMAD6（SMAD 家族成员 6）、JUN（Jun 原癌基因）、JAK2（Janus 激酶 2）、EP300（E1A 结合蛋白 p300）、ATF6（激活转录因子 6）、BTAF1（B-TFIID TATA 盒）结合蛋白相关因子 1)、BAFT（碱性亮氨酸拉链转录因子）、NOTCH1（神经源性位点缺口同源蛋白 1）、GATA3（GATA 结合蛋白 3）、SATB1（富含 AT 的特殊序列结合蛋白 1）、BMP7（骨形态发生）蛋白 7) 和 PPARG（过氧化物酶体增殖物激活受体 γ）能够识别 Th2 细胞向 Th9 细胞转化过程中显着差异改变的基因。我们识别了一些可以靶向 DEG 的常见 miR。关于代谢疾病中的 Th9 凸显了该领域的空白。我们的研究为探索Th9在各种代谢性疾病中的作用提供了理论依据，如糖尿病、糖尿病肾病、高血压、缺血性中风、脂肪性肝炎、肝纤维化、肥胖、腺癌、胶质母细胞瘤和神经胶质瘤、胃恶性肿瘤、黑色素瘤、神经母细胞瘤、骨肉瘤、胰腺癌、前列腺癌和胃癌。©Manoj Khokhar、Purvi Purohit、Ashita Gadwal、Sojit Tomo、Nitin Kumar Bajpai、Ravindra Shukla。最初发表于 JMIR 生物信息学和生物技术 (https://bioinform.jmir.org)，2023 年 2 月 23 日。

T helper (Th) 9 cells are a novel subset of Th cells that develop independently from Th2 cells and are characterized by the secretion of interleukin (IL)-9. Studies have suggested the involvement of Th9 cells in variable diseases such as allergic and pulmonary diseases (eg, asthma, chronic obstructive airway disease, chronic rhinosinusitis, nasal polyps, and pulmonary hypoplasia), metabolic diseases (eg, acute leukemia, myelocytic leukemia, breast cancer, lung cancer, melanoma, pancreatic cancer), neuropsychiatric disorders (eg, Alzheimer disease), autoimmune diseases (eg, Graves disease, Crohn disease, colitis, psoriasis, systemic lupus erythematosus, systemic scleroderma, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, atopic dermatitis, eczema), and infectious diseases (eg, tuberculosis, hepatitis). However, there is a dearth of information on its involvement in other metabolic, neuropsychiatric, and infectious diseases.This study aims to identify significant differentially altered genes in the conversion of Th2 to Th9 cells, and their regulating microRNAs (miRs) from publicly available Gene Expression Omnibus data sets of the mouse model using in silico analysis to unravel various pathogenic pathways involved in disease processes.Using differentially expressed genes (DEGs) identified from 2 publicly available data sets (GSE99166 and GSE123501) we performed functional enrichment and network analyses to identify pathways, protein-protein interactions, miR-messenger RNA associations, and disease-gene associations related to significant differentially altered genes implicated in the conversion of Th2 to Th9 cells.We extracted 260 common downregulated, 236 common upregulated, and 634 common DEGs from the expression profiles of data sets GSE99166 and GSE123501. Codifferentially expressed ILs, cytokines, receptors, and transcription factors (TFs) were enriched in 7 crucial Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology. We constructed the protein-protein interaction network and predicted the top regulatory miRs involved in the Th2 to Th9 differentiation pathways. We also identified various metabolic, allergic and pulmonary, neuropsychiatric, autoimmune, and infectious diseases as well as carcinomas where the differentiation of Th2 to Th9 may play a crucial role.This study identified hitherto unexplored possible associations between Th9 and disease states. Some important ILs, including CCL1 (chemokine [C-C motif] ligand 1), CCL20 (chemokine [C-C motif] ligand 20), IL-13, IL-4, IL-12A, and IL-9; receptors, including IL-12RB1, IL-4RA (interleukin 9 receptor alpha), CD53 (cluster of differentiation 53), CD6 (cluster of differentiation 6), CD5 (cluster of differentiation 5), CD83 (cluster of differentiation 83), CD197 (cluster of differentiation 197), IL-1RL1 (interleukin 1 receptor-like 1), CD101 (cluster of differentiation 101), CD96 (cluster of differentiation 96), CD72 (cluster of differentiation 72), CD7 (cluster of differentiation 7), CD152 (cytotoxic T lymphocyte-associated protein 4), CD38 (cluster of differentiation 38), CX3CR1 (chemokine [C-X3-C motif] receptor 1), CTLA2A (cytotoxic T lymphocyte-associated protein 2 alpha), CTLA28, and CD196 (cluster of differentiation 196); and TFs, including FOXP3 (forkhead box P3), IRF8 (interferon regulatory factor 8), FOXP2 (forkhead box P2), RORA (RAR-related orphan receptor alpha), AHR (aryl-hydrocarbon receptor), MAF (avian musculoaponeurotic fibrosarcoma oncogene homolog), SMAD6 (SMAD family member 6), JUN (Jun proto-oncogene), JAK2 (Janus kinase 2), EP300 (E1A binding protein p300), ATF6 (activating transcription factor 6), BTAF1 (B-TFIID TATA-box binding protein associated factor 1), BAFT (basic leucine zipper transcription factor), NOTCH1 (neurogenic locus notch homolog protein 1), GATA3 (GATA binding protein 3), SATB1 (special AT-rich sequence binding protein 1), BMP7 (bone morphogenetic protein 7), and PPARG (peroxisome proliferator-activated receptor gamma, were able to identify significant differentially altered genes in the conversion of Th2 to Th9 cells. We identified some common miRs that could target the DEGs. The scarcity of studies on the role of Th9 in metabolic diseases highlights the lacunae in this field. Our study provides the rationale for exploring the role of Th9 in various metabolic disorders such as diabetes mellitus, diabetic nephropathy, hypertensive disease, ischemic stroke, steatohepatitis, liver fibrosis, obesity, adenocarcinoma, glioblastoma and glioma, malignant neoplasm of stomach, melanoma, neuroblastoma, osteosarcoma, pancreatic carcinoma, prostate carcinoma, and stomach carcinoma.©Manoj Khokhar, Purvi Purohit, Ashita Gadwal, Sojit Tomo, Nitin Kumar Bajpai, Ravindra Shukla. Originally published in JMIR Bioinformatics and Biotechnology (https://bioinform.jmir.org), 23.02.2023.