Tokić Stana, Štefanić Mario, Karner Ivan, Glavaš-Obrovac Ljubica
Department of Molecular Diagnostics and Tissue Typing, Osijek University Hospital, Josipa Huttlera 4, HR-31000 Osijek, Croatia Department of Medicinal Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Osijek, Cara Hadrijana 10E, HR-31000 Osijek, Croatia.
Endokrynol Pol. 2017;68(3):274-828. doi: 10.5603/EP.2017.0020.
CD28/T-cell receptor (TCR)/cytotoxic T-lymphocyte antigen 4 (CTLA4) complex controls T-cell tolerance and autoimmunity in Hashimoto's thyroiditis (HT). In addition, CD45 protein tyrosine phosphatase (PTPase) and vitamin D receptor (VDR) cooperatively interact with the TCR complex to affect autoimmune processes central to the pathogenesis of HT. Nevertheless, their role in HT aetiology has been less well established. In this study, we aimed to explore mRNA expression levels of CTLA4, CD28, CD45, and VDR in T-cells, across different outcomes of HT.
The study included 45 HT patients and 13 euthyroid, healthy controls. T-lymphocytes were isolated from peripheral blood mononuclear cells, total mRNA was extracted from T-cells, and gene expression was studied by reverse transcription-polymerase chain reaction (RT-PCR) and ImageQuant method relative to glyceraldehyde-3-phosphate dehydrogenase RT-PCR products.
Nominally higher expression levels of VDR, CTLA4, CD28, and CD45RAB mRNA were found in unsorted T-lymphocytes of healthy controls when compared to the HT patients. No difference was observed between hypothyroid/untreated, spontaneously euthyroid and LT4-treated HT patients. VDR mRNA expression was linked to both T3 levels and CTLA4 gene expression, whilst CD45RB mRNA expression coincided with CTLA4 and CD28 transcript levels. Conversely, older age and lower T3 levels were associated with increased abundance of CD45R0 isoform in HT patients.
The results suggest a cross talk between endocrine and immune functions in HT pathology: an altered peripheral T cell mRNA profile with reduced VDR, CTLA4, CD28, and CD45RAB transcript levels is accompanied by age-related shift from naive to memory/late-differentiated T cell CD45R mRNA signature and associated with thyroid hormone status in the HT patients.
CD28/T细胞受体（TCR）/细胞毒性T淋巴细胞相关抗原4（CTLA4）复合物控制着桥本甲状腺炎（HT）中的T细胞耐受性和自身免疫。此外，CD45蛋白酪氨酸磷酸酶（PTPase）和维生素D受体（VDR）与TCR复合物协同相互作用，以影响HT发病机制核心的自身免疫过程。然而，它们在HT病因学中的作用尚未完全明确。在本研究中，我们旨在探讨HT不同结局下T细胞中CTLA4、CD28、CD45和VDR的mRNA表达水平。
该研究纳入了45例HT患者和13例甲状腺功能正常的健康对照。从外周血单核细胞中分离出T淋巴细胞，从T细胞中提取总mRNA，并通过逆转录-聚合酶链反应（RT-PCR）和ImageQuant方法相对于甘油醛-3-磷酸脱氢酶RT-PCR产物研究基因表达。
与HT患者相比，健康对照未分选的T淋巴细胞中VDR、CTLA4、CD28和CD45RAB mRNA的表达水平名义上更高。甲状腺功能减退/未治疗、自发甲状腺功能正常和接受左甲状腺素（LT4）治疗的HT患者之间未观察到差异。VDR mRNA表达与T3水平和CTLA4基因表达均相关，而CD45RB mRNA表达与CTLA4和CD28转录水平一致。相反，在HT患者中，年龄较大和T3水平较低与CD45R0异构体丰度增加有关。
结果表明HT病理中内分泌和免疫功能之间存在相互作用：外周T细胞mRNA谱改变，VDR、CTLA4、CD28和CD45RAB转录水平降低，同时伴随着与年龄相关的从初始T细胞向记忆/晚期分化T细胞CD45R mRNA特征的转变，并与HT患者的甲状腺激素状态相关。
