巴西 1 型糖尿病患者的调节性 CD4+CD25+Foxp3+T 细胞中近期胸腺移居者的频率降低

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-04-09 DOI:10.1016/j.imlet.2024.106857
Jeane de Souza Nogueira , Thamires Rodrigues Gomes , Danielle Angst Secco , Inez Silva de Almeida , Alessandra Saldanha Matheus Fernandes da Costa , Roberta Arnoldi Cobas , Gilson Costa dos Santos Jr , Marília Brito Gomes , Luís Cristóvão Porto
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引用次数: 0

摘要

为了控制免疫反应,调节性 CD4+CD25+Foxp3+ T 细胞(Treg)通过胸腺新移民(RTE)的不断到来来维持其广泛而多样的细胞库。然而,在青春期,随着胸腺的自然消退,RTE 的活性开始下降,从而给Treg细胞群带来了尚未完全描述的后果。1 型糖尿病(T1D)患者的 Treg 细胞在数量和质量上都出现了损伤。我们的目的是评估两个不同年龄组(年轻人和成年人)T1D 患者的外周 Treg 和 RTE 细胞频率,并验证 HLA 表型是否与之相关。为此,我们用流式细胞术分析了巴西 20 名已确诊 T1D 患者(12 名年轻人和 8 名成年人)和 21 名健康对照者(11 名年轻人和 10 名成年人)的血液样本,以验证其中 CD4、Treg(CD4+CD25+Foxp3+)以及 CD45RA+(幼稚)和 CD31+(RTE)亚群的百分比。此外,还设定了 HLA 分型。我们观察到,年轻的 T1D 患者的 Treg 细胞总数和 Treg 细胞中的 naive RTE 频率都有所下降。我们还发现,在 T1D 患者中,与风险相关的 HLA 等位基因具有显著的普遍性。在进行多变量分析时,我们证实所述的细胞变化提供了将 T1D 患者与对照组区分开来的重要变量。我们的数据共同凸显了 T1D 患者(尤其是年轻患者)Treg 细胞平衡失调和疾病预后的相关方面,这可能有助于未来涉及 Treg 细胞操作的治疗策略。
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Type 1 Diabetes Brazilian patients exhibit reduced frequency of recent thymic emigrants in regulatory CD4+CD25+Foxp3+T cells

To control immune responses, regulatory CD4+CD25+Foxp3+ T cells (Treg) maintain their wide and diverse repertoire through continuous arrival of recent thymic emigrants (RTE). However, during puberty, the activity of RTE starts to decline as a natural process of thymic involution, introducing consequences, not completely described, to the repertoire. Type 1 diabetes (T1D) patients show quantitative and qualitative impairments on the Treg cells. Our aim was to evaluate peripheral Treg and RTE cell frequencies, in T1D patients from two distinct age groups (young and adults) and verify if HLA phenotypes are concomitant associated. To this, blood samples from Brazilian twenty established T1D patients (12 young and 8 adults) and twenty-one healthy controls (11 young and 10 adults) were analyzed, by flow cytometry, to verify the percentages of CD4, Treg (CD4+CD25+Foxp3+) and the subsets of CD45RA+ (naive) and CD31+(RTE) within then. Furthermore, the HLA typing was also set. We observed that the young established T1D patients feature decreased frequencies in total Treg cells and naive RTE within Treg cells. Significant prevalence of HLA alleles, associated with risk, in T1D patients, was also identified. Performing a multivariate analysis, we confirmed that the cellular changes described offers significant variables that distinct T1D patients from the controls. Our data collectively highlight relevant aspects about homeostasis imbalances in the Treg cells of T1D patients, especially in young, and disease prognosis; that might contribute for future therapeutic strategies involving Treg cells manipulation.

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4.30%
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