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特应性中 T 细胞表型与维生素 D 受体和维生素 D 结合蛋白基因多态性的关系。

Relation of T Cell Profile with Vitamin D Receptor and Vitamin D-Binding Protein Gene Polymorphisms in Atopy.

机构信息

Department of Immunology and Allergology, Lithuanian University of Health Sciences, 50161 Kaunas, Lithuania.

Laboratory of Immunology, Department of Immunology and Allergology, Lithuanian University of Health Sciences, 50161 Kaunas, Lithuania.

出版信息

Int J Mol Sci. 2024 Aug 20;25(16):9021. doi: 10.3390/ijms25169021.

Abstract

Atopic diseases, including atopic dermatitis (AD) and allergic asthma (AA), are characterized by complex immune responses involving various T cells subsets and their cytokine profiles. It is assumed that single nucleotide polymorphisms (SNPs) in the Vitamin D receptor () gene and the Vitamin D-binding protein () gene are related to the action of Vitamin D and, consequently, play a role in regulating the immune response. However, there is not enough data to unequivocally support the hypothesis about the relationship between T cells profile and or SNPs. Two hundred sixty-six subjects (aged > 18 years) were involved in the study: 100 patients with mild or moderate AD, 85 patients with mild or moderate AA, and 81 healthy individuals. Blood cell counts were determined by standard methods. Flow cytometric analysis was used to evaluate CD4 T-helper (Th) cell subtypes: Th2, Th1, Th17, and T regulatory (Treg) cells in peripheral blood. Measurements of cytokines, total immunoglobulin E (IgE), and Vitamin D levels in serum were evaluated by ELISA. Significantly higher levels of Th1, Th2, and Th17 cells, along with lower levels of Tregs, were found in patients with atopic diseases compared to healthy individuals. Additionally, higher serum levels of interleukin (IL) 5, IL-17A, and transforming growth factor-β1 (TGF-β1), as well as lower levels of IL-10, were observed in patients with atopic diseases than in control. The study established associations between SNPs and immune profiles: the AA genotype of rs731236 was associated with increased Th2 and Th17 cells and a higher Th1/Th2 ratio; the GG genotype of rs731236 was linked to decreased serum IL-10 and TGF-β1 levels; and the TT genotype of rs11168293 was associated with increased IL-10 levels. Additionally, the GG genotype of gene SNP rs4588 was associated with reduced Th2 and Th17 lymphocytes, while the TT genotype of rs4588 was linked to decreased IL-10 levels. Furthermore, the CC genotype of rs7041 was associated with higher levels of Th2, Th17, IL-10, and IL-35, as well as reduced levels of TGF-β1, while the GG genotype of rs3733359 was associated with reduced IL-10 levels. In conclusion, our study demonstrates that the Vitamin D receptor gene single nucleotide polymorphisms rs731236 and rs11168293, along with polymorphisms in the Vitamin D-binding protein gene (rs4588, rs7041, rs3733359), are significantly associated with variations in T cell profiles in atopy. These variations may play a crucial role in promoting inflammation and provide insight into the genetic factors contributing to the pathogenesis of atopy.

摘要

特应性疾病,包括特应性皮炎(AD)和过敏性哮喘(AA),其特征是涉及各种 T 细胞亚群及其细胞因子谱的复杂免疫反应。据假设,维生素 D 受体()基因和维生素 D 结合蛋白()基因中的单核苷酸多态性(SNPs)与维生素 D 的作用有关,因此在调节免疫反应中发挥作用。然而,没有足够的数据明确支持 T 细胞谱与或 SNPs 之间存在关系的假设。研究纳入了 266 名(年龄>18 岁)受试者:100 名轻度或中度 AD 患者,85 名轻度或中度 AA 患者和 81 名健康个体。采用标准方法测定血细胞计数。采用流式细胞术分析评估外周血中 CD4 T 辅助(Th)细胞亚型:Th2、Th1、Th17 和 T 调节(Treg)细胞。通过 ELISA 评估血清细胞因子、总免疫球蛋白 E(IgE)和维生素 D 水平。与健康个体相比,特应性疾病患者的 Th1、Th2 和 Th17 细胞水平显著升高,而 Treg 细胞水平降低。此外,特应性疾病患者的血清白细胞介素(IL)5、IL-17A 和转化生长因子-β1(TGF-β1)水平较高,而 IL-10 水平较低。研究还发现,与 rs731236 的 AA 基因型相关的 Th2 和 Th17 细胞增加和 Th1/Th2 比值升高;rs731236 的 GG 基因型与血清 IL-10 和 TGF-β1 水平降低有关;rs11168293 的 TT 基因型与 IL-10 水平升高有关。此外,基因 SNP rs4588 的 GG 基因型与 Th2 和 Th17 淋巴细胞减少有关,而 rs4588 的 TT 基因型与 IL-10 水平降低有关。此外,rs7041 的 CC 基因型与 Th2、Th17、IL-10 和 IL-35 水平升高以及 TGF-β1 水平降低有关,而 rs3733359 的 GG 基因型与 IL-10 水平降低有关。总之,我们的研究表明,维生素 D 受体基因的单核苷酸多态性 rs731236 和 rs11168293 以及维生素 D 结合蛋白基因的多态性(rs4588、rs7041、rs3733359)与特应性中 T 细胞谱的变化显著相关。这些变化可能在促进炎症中发挥关键作用,并深入了解特应性发病机制中的遗传因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c7e/11354884/5ca3609122ab/ijms-25-09021-g001.jpg

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