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Curr Mol Med. 2018;18(2):83-90. doi: 10.2174/1566524018666180705105753.

Decreased Expression of TIM-3 on Th17 Cells Associated with Ophthalmopathy in Patients with Graves' Disease.

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State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Department of Endocrinology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Department of Ophthalmology and Visual Science, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.



Thyroid-associated Ophthalmopathy (TAO) is one of the most common orbital immunological diseases in adults. CD4+ helper T (Th) cells play important roles in the pathogenesis of TAO. But the mechanisms regulating CD4+ T cell activity is unclear. This study examines T cell immunoglobulin domain and mucin domain 3 (TIM-3) expression in helper T cell type 1 (Th1), Th17, and regulatory T cells in sufferers of TAO.


Participants were divided into 3 groups: patients with TAO, patients with Graves' disease but without orbitopathy (GD), and healthy control patients (HC). Peripheral blood samples were collected for each patient in the designated group. Flow cytometry methods assessed the frequency of Th1 (CD4+IFN-γ+), Th17 (CD4+IL-17+), regulatory T cells (CD4+CD25hiCD127lo), and TIM-3 protein expression. Mean fluorescence intensity (MFI) measured the magnitude of TIM-3 expression and the percentage of TIM-3+ cells for each patient.


Compared to the GD group, TAO patients possessed higher frequencies of Th1 and Th17 cells in peripheral blood samples. The percentage of TIM-3+ Th1 and Th17 cells was significantly lower in the TAO patients than the GD group. Across all patients sampled, TIM-3+ cell percentage negatively correlated with Th1 cell frequency. Th1 and Th17 cells exhibited significantly decreased expression of TIM-3 in TAO patients compared to healthy controls. Regulatory T cells showed little TIM-3 expression and we observed no significant differences in frequency between groups.


These results suggest a role for TIM-3 in the regulation of Th1 and Th17 cells and the pathogenesis of Graves' ophthalmopathy.


CD4+ helper T cells; Graves’ disease; T cell immunoglobulin domain and mucin domain 3; Thyroid-associated Ophthalmopathy; autoimmune thyroid disease; immune tolerance.

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