{"title":"Th9和Treg细胞稳态和细胞因子动力学在糖尿病肾病进展中的免疫学作用。","authors":"Manoj Khokhar, Purvi Purohit, Ashita Gadwal, Nitin Kumar Bajpai, Ravindra Kumar Shukla","doi":"10.1080/08830185.2025.2515836","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>T cells play a crucial role in immune responses and are involved in chronic diseases such as Type 2 Diabetes Mellitus (T2DM) and its complications, including Diabetic Nephropathy (DN). Among these, regulatory T cells (Treg) act as key regulators, while T helper 9 (Th9) cells, which produce IL-9, are essential in maintaining immune balance.</p><p><strong>Methods: </strong>The study included 145 participants divided into four groups: T2DM with nephropathy (35), T2DM without nephropathy (35), non-diabetic chronic kidney disease (ND-CKD) (35), and healthy controls (35). Various assessments were conducted, including anthropometric measurements, biochemical analyses, gene expression analysis was performed using RT-qPCR to profile mRNA and miRNA expression levels, flow cytometry (immune cell populations), and cytokine analysis by ELISA. Statistical analyses were carried out using SPSS, jamovi, Orange Data Mining, and Excel, ensuring robust evaluation and interpretation of the data.</p><p><strong>Results: </strong>Th9 cells correlated with IL-9 (<i>r</i> = 0.72, <i>p</i> < 0.01), and Treg cells with IL-10 (<i>r</i> = 0.68, <i>p</i> < 0.01). The Th9/Treg ratio significantly increased across groups (χ<sup>2</sup> = 14.8, <i>p</i> < 0.001), with notable differences between HC and T2DM (<i>p</i> = 0.009) and HC and DN (<i>p</i> < 0.001). IL-9 (AUC = 0.880) and Th9/Treg ratio (AUC = 0.762) showed potential as DN diagnostic markers. PTEN levels were reduced in DN and ND-CKD (<i>p</i> < 0.001, <i>p</i> = 0.017), while MMP2, hsa-miR-21-5p, and hsa-miR-181b-5p were elevated in disease groups (all <i>p</i> < 0.001), correlating with renal markers. COL4A4 was higher in DN vs. HC (<i>p</i> = 0.004), with PTEN downregulation linked to immune imbalance and fibrosis.</p><p><strong>Conclusion: </strong>Our study unveils immune cell and cytokine intricacies in DN. The high Th9/Treg ratio in T2DM and DN suggests immune tolerance loss, potentially influencing DN development. IL-9 and IL-10 display diagnostic potential. The Th9/Treg ratio and IL-9 serves as a discriminative diagnostic marker, particularly in DN. These insights offer avenues for early DN diagnosis and management.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-25"},"PeriodicalIF":2.9000,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Immunological insights into role of Th9 and Treg cell homeostasis and cytokines dynamics in the progression of diabetic nephropathy.\",\"authors\":\"Manoj Khokhar, Purvi Purohit, Ashita Gadwal, Nitin Kumar Bajpai, Ravindra Kumar Shukla\",\"doi\":\"10.1080/08830185.2025.2515836\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>T cells play a crucial role in immune responses and are involved in chronic diseases such as Type 2 Diabetes Mellitus (T2DM) and its complications, including Diabetic Nephropathy (DN). Among these, regulatory T cells (Treg) act as key regulators, while T helper 9 (Th9) cells, which produce IL-9, are essential in maintaining immune balance.</p><p><strong>Methods: </strong>The study included 145 participants divided into four groups: T2DM with nephropathy (35), T2DM without nephropathy (35), non-diabetic chronic kidney disease (ND-CKD) (35), and healthy controls (35). Various assessments were conducted, including anthropometric measurements, biochemical analyses, gene expression analysis was performed using RT-qPCR to profile mRNA and miRNA expression levels, flow cytometry (immune cell populations), and cytokine analysis by ELISA. Statistical analyses were carried out using SPSS, jamovi, Orange Data Mining, and Excel, ensuring robust evaluation and interpretation of the data.</p><p><strong>Results: </strong>Th9 cells correlated with IL-9 (<i>r</i> = 0.72, <i>p</i> < 0.01), and Treg cells with IL-10 (<i>r</i> = 0.68, <i>p</i> < 0.01). The Th9/Treg ratio significantly increased across groups (χ<sup>2</sup> = 14.8, <i>p</i> < 0.001), with notable differences between HC and T2DM (<i>p</i> = 0.009) and HC and DN (<i>p</i> < 0.001). IL-9 (AUC = 0.880) and Th9/Treg ratio (AUC = 0.762) showed potential as DN diagnostic markers. PTEN levels were reduced in DN and ND-CKD (<i>p</i> < 0.001, <i>p</i> = 0.017), while MMP2, hsa-miR-21-5p, and hsa-miR-181b-5p were elevated in disease groups (all <i>p</i> < 0.001), correlating with renal markers. COL4A4 was higher in DN vs. HC (<i>p</i> = 0.004), with PTEN downregulation linked to immune imbalance and fibrosis.</p><p><strong>Conclusion: </strong>Our study unveils immune cell and cytokine intricacies in DN. The high Th9/Treg ratio in T2DM and DN suggests immune tolerance loss, potentially influencing DN development. IL-9 and IL-10 display diagnostic potential. The Th9/Treg ratio and IL-9 serves as a discriminative diagnostic marker, particularly in DN. 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引用次数: 0
摘要
背景：T细胞在免疫应答中起着至关重要的作用，并参与慢性疾病，如2型糖尿病（T2DM）及其并发症，包括糖尿病肾病（DN）。其中，调节性T细胞（Treg）起着关键的调节作用，而产生IL-9的辅助性T细胞（Th9）在维持免疫平衡中至关重要。方法：该研究纳入145名参与者，分为四组：伴有肾病的T2DM（35人）、无肾病的T2DM（35人）、非糖尿病性慢性肾病（ND-CKD）（35人）和健康对照组（35人）。进行了各种评估，包括人体测量、生化分析、使用RT-qPCR进行基因表达分析以分析mRNA和miRNA表达水平、流式细胞术（免疫细胞群）和ELISA进行细胞因子分析。使用SPSS、jamovi、Orange Data Mining和Excel进行统计分析，确保对数据进行可靠的评估和解释。结果：Th9细胞与IL-9 （r = 0.72, p r = 0.68, p 2 = 14.8, p p = 0.009）、HC和DN （p p = 0.017）相关，MMP2、hsa-miR-21-5p、hsa-miR-181b-5p在疾病组中升高（p均= 0.004），PTEN下调与免疫失衡和纤维化有关。结论：我们的研究揭示了DN中免疫细胞和细胞因子的复杂性。T2DM和DN的高Th9/Treg比值提示免疫耐受丧失，可能影响DN的发展。IL-9和IL-10显示诊断潜力。Th9/Treg比率和IL-9可作为鉴别诊断标志物，特别是在DN中。这些见解为DN的早期诊断和管理提供了途径。
Immunological insights into role of Th9 and Treg cell homeostasis and cytokines dynamics in the progression of diabetic nephropathy.
Background: T cells play a crucial role in immune responses and are involved in chronic diseases such as Type 2 Diabetes Mellitus (T2DM) and its complications, including Diabetic Nephropathy (DN). Among these, regulatory T cells (Treg) act as key regulators, while T helper 9 (Th9) cells, which produce IL-9, are essential in maintaining immune balance.
Methods: The study included 145 participants divided into four groups: T2DM with nephropathy (35), T2DM without nephropathy (35), non-diabetic chronic kidney disease (ND-CKD) (35), and healthy controls (35). Various assessments were conducted, including anthropometric measurements, biochemical analyses, gene expression analysis was performed using RT-qPCR to profile mRNA and miRNA expression levels, flow cytometry (immune cell populations), and cytokine analysis by ELISA. Statistical analyses were carried out using SPSS, jamovi, Orange Data Mining, and Excel, ensuring robust evaluation and interpretation of the data.
Results: Th9 cells correlated with IL-9 (r = 0.72, p < 0.01), and Treg cells with IL-10 (r = 0.68, p < 0.01). The Th9/Treg ratio significantly increased across groups (χ2 = 14.8, p < 0.001), with notable differences between HC and T2DM (p = 0.009) and HC and DN (p < 0.001). IL-9 (AUC = 0.880) and Th9/Treg ratio (AUC = 0.762) showed potential as DN diagnostic markers. PTEN levels were reduced in DN and ND-CKD (p < 0.001, p = 0.017), while MMP2, hsa-miR-21-5p, and hsa-miR-181b-5p were elevated in disease groups (all p < 0.001), correlating with renal markers. COL4A4 was higher in DN vs. HC (p = 0.004), with PTEN downregulation linked to immune imbalance and fibrosis.
Conclusion: Our study unveils immune cell and cytokine intricacies in DN. The high Th9/Treg ratio in T2DM and DN suggests immune tolerance loss, potentially influencing DN development. IL-9 and IL-10 display diagnostic potential. The Th9/Treg ratio and IL-9 serves as a discriminative diagnostic marker, particularly in DN. These insights offer avenues for early DN diagnosis and management.
期刊介绍：
This review journal provides the most current information on basic and translational research in immunology and related fields. In addition to invited reviews, the journal accepts for publication articles and editorials on relevant topics proposed by contributors. Each issue of International Reviews of Immunology contains both solicited and unsolicited review articles, editorials, and ''In-this-Issue'' highlights. The journal also hosts reviews that position the authors'' original work relative to advances in a given field, bridging the gap between annual reviews and the original research articles.
This review series is relevant to all immunologists, molecular biologists, microbiologists, translational scientists, industry researchers, and physicians who work in basic and clinical immunology, inflammatory and allergic diseases, vaccines, and additional topics relevant to medical research and drug development that connect immunology to disciplines such as oncology, cardiovascular disease, and metabolic disorders.
Covered in International Reviews of Immunology: Basic and developmental immunology (innate and adaptive immunity; inflammation; and tumor and microbial immunology); Clinical research (mechanisms of disease in man pertaining to infectious diseases, autoimmunity, allergy, oncology / immunology); and Translational research (relevant to biomarkers, diagnostics, vaccines, and drug development).
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