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

Abstract

Purpose: 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.Methods: 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.Results: 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.Conclusion: These results suggest a role for TIM-3 in the regulation of Th1 and Th17 cells and the pathogenesis of Graves’ ophthalmopathy.

Circulating T Cells Exhibit Different TIM3/Galectin-9 Expression in Patients with Obesity and Obesity-Related Diabetes

“…In our study, plasma galectin-9 levels in patients with obesity comorbid type 2 diabetes significantly increased and positively correlated with weight, BMI, hipline, UA, and especially islet-related indicators insulin and C-peptides. These results were different with those from patients with T2DM and chronic kidney disease [ 8 ]. It may be due to the inflammatory status of obese-associated insulin resistance, as well as the alteration of the immune response of the patients with obesity comorbid T2DM.…”

“…By binding to its ligand galectin-9, TIM3 can induce T cell exhaustion and tolerance [ 6 , 7 ]. Increasing evidence showed the vital role of the interaction of TIM3 and galectin-9 in several chronic diseases, such as cancer, hepatitis, and autoimmune diseases [ 8 , 9 ]. The physiological role of TIM3 has been implicated in both stimulatory and inhibitory functions [ 10 , 11 ].…”

Th17/Treg‑cell balance in the peripheral blood of pregnant females with a history of recurrent spontaneous abortion receiving progesterone or cyclosporine A

“…In addition to the signal from antigen recognition, T-cell activation requires a second signal from co-stimulatory molecules, which maybe either positive or negative (12,13). Among the inhibitory co-stimulatory molecules, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T-cell immunoglobulin mucin-3 (Tim-3) and programmed cell death-1 (PD-1) have attracted much attention regarding their roles in regulating Th17-and Treg-cell function to maintain a balanced immune response (14)(15)(16)(17). For instance, Tim-3 has been associated with a shift in the balance from Th17 and Treg cells to Treg dominance (16).…”

Bidirectional regulation between 1st trimester HTR8/SVneo trophoblast cells and in vitro differentiated Th17/Treg cells suggest a fetal‐maternal regulatory loop in human pregnancy

“…Inhibitory molecules such as CTLA‐4, Tim‐3, or PD‐1, play a role in regulating Th17 and Treg cell function to maintain a balanced immune response . For example, Tim‐3 has been associated with a shift in the balance from Th17 and Treg cells to Treg dominance .…”