Štefanić Mario, Tokić Stana, Suver-Stević Mirjana, Glavaš-Obrovac Ljubica
Department of Nuclear Medicine and Oncology, Faculty of Medicine, University of Osijek, Osijek, Croatia.
Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Osijek, Osijek, Croatia.
Exp Clin Endocrinol Diabetes. 2019 May;127(5):281-288. doi: 10.1055/a-0597-8948. Epub 2018 Jun 11.
Co-inhibitory receptors (IR), such as TIGIT and FCRL3, provide a checkpoint against highly destructive immune responses. Co-expression of TIGIT and FCRL3, in particular, has been linked to the HELIOS subset of regulatory CD4FOXP3T-cells. Of these, CD4FOXP3-exon(E)2 cells have higher expression of IR and exhibit strongest suppressive properties. Nevertheless, how the expression of TIGIT, FCRL3, HELIOS, and FOXP3E2 is regulated in chronic autoimmune thyroiditis (AT), is not known.
Thirty patients with AT [encompassing spontaneously euthyroid (euAT), hypothyroid-untreated and L-thyroxine-treated cases)] and 10 healthy controls (HC) were recruited. FCRL3, TIGIT, HELIOS and FOXP3E2 mRNA expression levels in peripheral blood (PB) T cells were measured via quantitative real-time PCR and compared to clinicopathological factors.
The TIGIT and FCRL3 expression levels from T cells of AT cases were inversely related to the thyroid volume, and were significantly increased in hypothyroid patients (on+off L-thyroxine), but not euAT cases. The FCRL3 expression in PB T cells positively correlated with thyroid-peroxidase autoantibody levels; by contrast, T cells from aged AT patients and combined samples (AT+HC) accumulated more TIGIT mRNA. The patients with higher TIGIT mRNA levels had a greater prevalence of hypothyroidism, showing higher peak thyrotropin levels at diagnosis or at follow-up.
Multiple IR, namely FCRL3 and TIGIT, but not the transcription factors HELIOS and FOXP3E2, showed increased mRNA levels in PB T cells from end-stage, long-standing and/or more aggressive AT, in proportion to disease severity. A relation with major clinical subphenotypes was observed, thereby identifying IR as potentially important players in AT.
共抑制受体（IR），如TIGIT和FCRL3，对高度破坏性的免疫反应起到检查点作用。特别是TIGIT和FCRL3的共表达与调节性CD4FOXP3T细胞的HELIOS亚群有关。其中，CD4FOXP3外显子（E）2细胞具有更高的IR表达，并表现出最强的抑制特性。然而，在慢性自身免疫性甲状腺炎（AT）中，TIGIT、FCRL3、HELIOS和FOXP3E2的表达是如何调控的尚不清楚。
招募了30例AT患者[包括自发甲状腺功能正常（euAT）、未经治疗的甲状腺功能减退和左甲状腺素治疗的病例]和10名健康对照（HC）。通过定量实时PCR测量外周血（PB）T细胞中FCRL3、TIGIT、HELIOS和FOXP3E2 mRNA表达水平，并与临床病理因素进行比较。
AT患者T细胞中TIGIT和FCRL3表达水平与甲状腺体积呈负相关，在甲状腺功能减退患者（左甲状腺素治疗和未治疗）中显著升高，但在euAT患者中未升高。PB T细胞中FCRL3表达与甲状腺过氧化物酶自身抗体水平呈正相关；相比之下，老年AT患者和合并样本（AT+HC）的T细胞积累了更多的TIGIT mRNA。TIGIT mRNA水平较高的患者甲状腺功能减退的患病率更高，在诊断或随访时促甲状腺激素水平峰值更高。
多种IR，即FCRL3和TIGIT，但不是转录因子HELIOS和FOXP3E2，在晚期、长期和/或更具侵袭性的AT患者的PB T细胞中，mRNA水平升高，与疾病严重程度成正比。观察到与主要临床亚表型的关系，从而确定IR是AT中潜在的重要参与者。
