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Abstract：
UNASSIGNED: T-cell immunoglobulin and mucin domain (Tim) proteins are immunomodulatory molecules that play key roles in the regulation of T-cell activation. Published studies have reported that Tim molecules are involved in the pathogenesis of certain autoimmune diseases. Type 1 diabetes (T1D) is an autoimmune disease in which T cells mediate the destruction of islet β cells. However, the expression of Tim molecules in T1D remains unclear. In this study, we measured the expression of Tim family molecules as well as T-cell subset-specific transcription factors in T1D patients, and we explored the possible involvement of Tim molecules in the pathogenesis of T1D.
UNASSIGNED: Ninety T1D patients, Thirty-six type 2 diabetes (T2D) patients and forty healthy controls (HCs) were recruited for this study. Peripheral blood mononuclear cells (PBMCs) were isolated, RNA was extracted from the PBMCs and reverse transcribed into cDNA, and gene expression patterns were analysed by RT-qPCR. The expression of Tim molecules in different T-cell subsets was analysed by flow cytometry.
UNASSIGNED: Compared with that in HCs, the mRNA expression of Tim-1 and RORC was increased in T1D patients (P=0.0355 and P=0.0423, respectively), while the expression of Tim-3 was decreased (P=0.0013). In addition, compared with HCs, the ratio of Tim-3 to Tim-1 expression in diabetic patients was decreased (P<0.0001 for T1D and P=0.0387 for T2D). The ratios of T-Bet to GATA3 expression and RORC to FOXP3 expression were higher in T1D patients than in HCs (P=0.0042 and P=0.0066, respectively). Furthermore, the T1D patients with defective islet function had more significant imbalances in the Tim-3/Tim-1 and RORC/FOXP3 ratios (P<0.0001, and P=0.001, respectively). Moreover, Both Tim-3 expression in CD4+ T cells and the Tim-3 to Tim-1 ratio were elevated in T1D in the remission phase compared to T1D.
UNASSIGNED: Our study revealed altered expression of Tim molecules in T1D patients. The imbalanced ratios of Tim-3/Tim-1 expression were more pronounced in T1D patients with defective islet function. However, alterations in Tim molecule expression are mitigated in T1D in the remission phase. All these findings suggest that Tim family molecules may be involved in the pathogenesis of T1D.
UNASSIGNED: Ninety T1D patients, Thirty-six type 2 diabetes (T2D) patients and forty healthy controls (HCs) were recruited for this study. Peripheral blood mononuclear cells (PBMCs) were isolated, RNA was extracted from the PBMCs and reverse transcribed into cDNA, and gene expression patterns were analysed by RT-qPCR. The expression of Tim molecules in different T-cell subsets was analysed by flow cytometry.
UNASSIGNED: Compared with that in HCs, the mRNA expression of Tim-1 and RORC was increased in T1D patients (P=0.0355 and P=0.0423, respectively), while the expression of Tim-3 was decreased (P=0.0013). In addition, compared with HCs, the ratio of Tim-3 to Tim-1 expression in diabetic patients was decreased (P<0.0001 for T1D and P=0.0387 for T2D). The ratios of T-Bet to GATA3 expression and RORC to FOXP3 expression were higher in T1D patients than in HCs (P=0.0042 and P=0.0066, respectively). Furthermore, the T1D patients with defective islet function had more significant imbalances in the Tim-3/Tim-1 and RORC/FOXP3 ratios (P<0.0001, and P=0.001, respectively). Moreover, Both Tim-3 expression in CD4+ T cells and the Tim-3 to Tim-1 ratio were elevated in T1D in the remission phase compared to T1D.
UNASSIGNED: Our study revealed altered expression of Tim molecules in T1D patients. The imbalanced ratios of Tim-3/Tim-1 expression were more pronounced in T1D patients with defective islet function. However, alterations in Tim molecule expression are mitigated in T1D in the remission phase. All these findings suggest that Tim family molecules may be involved in the pathogenesis of T1D.
摘要：
T细胞免疫球蛋白和粘蛋白结构域(Tim)蛋白是在T细胞活化的调节中起关键作用的免疫调节分子。已发表的研究报道Tim分子参与某些自身免疫性疾病的发病机理。1型糖尿病（T1D）是一种自身免疫性疾病，其中T细胞介导胰岛β细胞的破坏。然而,T1D中Tim分子的表达尚不清楚.在这项研究中,我们测量了T1D患者中Tim家族分子和T细胞亚群特异性转录因子的表达,我们探讨了Tim分子可能参与T1D的发病机制。
90名T1D患者，本研究招募了36名2型糖尿病（T2D）患者和40名健康对照（HC）。分离外周血单核细胞（PBMC），从PBMC中提取RNA并逆转录为cDNA,通过RT-qPCR分析基因表达模式。通过流式细胞术分析Tim分子在不同T细胞亚群中的表达。
与HC相比，T1D患者Tim-1和RORC的mRNA表达增加(P=0.0355和P=0.0423),Tim-3的表达降低(P=0.0013)。此外,与HC相比，糖尿病患者Tim-3与Tim-1表达的比率降低（T1DP<0.0001，T2DP=0.0387）。T1D患者的T-Bet与GATA3表达和RORC与FOXP3表达的比率高于HC（分别为P=0.0042和P=0.0066）。此外，胰岛功能缺陷的T1D患者的Tim-3/Tim-1和RORC/FOXP3比值失衡更为显著(分别为P<0.0001和P=0.001).此外，与T1D相比,在缓解期的T1D中,CD4+T细胞中的Tim-3表达和Tim-3与Tim-1的比率均升高。
我们的研究揭示了T1D患者中Tim分子表达的改变。在胰岛功能缺陷的T1D患者中，Tim-3/Tim-1表达的失衡比更为明显。然而,Tim分子表达的改变在T1D缓解期得到缓解。所有这些发现表明Tim家族分子可能参与了T1D的发病机理。
90名T1D患者，本研究招募了36名2型糖尿病（T2D）患者和40名健康对照（HC）。分离外周血单核细胞（PBMC），从PBMC中提取RNA并逆转录为cDNA,通过RT-qPCR分析基因表达模式。通过流式细胞术分析Tim分子在不同T细胞亚群中的表达。
与HC相比，T1D患者Tim-1和RORC的mRNA表达增加(P=0.0355和P=0.0423),Tim-3的表达降低(P=0.0013)。此外,与HC相比，糖尿病患者Tim-3与Tim-1表达的比率降低（T1DP<0.0001，T2DP=0.0387）。T1D患者的T-Bet与GATA3表达和RORC与FOXP3表达的比率高于HC（分别为P=0.0042和P=0.0066）。此外，胰岛功能缺陷的T1D患者的Tim-3/Tim-1和RORC/FOXP3比值失衡更为显著(分别为P<0.0001和P=0.001).此外，与T1D相比,在缓解期的T1D中,CD4+T细胞中的Tim-3表达和Tim-3与Tim-1的比率均升高。
我们的研究揭示了T1D患者中Tim分子表达的改变。在胰岛功能缺陷的T1D患者中，Tim-3/Tim-1表达的失衡比更为明显。然而,Tim分子表达的改变在T1D缓解期得到缓解。所有这些发现表明Tim家族分子可能参与了T1D的发病机理。
