The expression of Tim-1 and Tim-4 molecules in regulatory T cells in type 1 diabetes

The TIM family comprises of eight genes in the mouse, three of which are conserved in humans (TIM-1, TIM-3, and TIM-4). Previous studies have revealed the relationships between Tim3⁺ Tregs and autoimmune disease. There was little study about the expression of Tim1 and Tim4 surface molecules on Tregs. We evaluated the frequency of the Tim1⁺Tregs and Tim4⁺Tregs in type 1 diabetes (T1D) in the present study.

A total of 28 patients with T1D and 14 gender-, age-, and ethnically matched healthy volunteers were recruited. PBMCs from these individuals were isolated and analyzed by flow cytometry. Splenocytes from mice were also analyzed by flow cytometry.

There is no difference in the frequency of Treg cells in peripheral blood isolated from T1D patients. Tim1 on CD4⁺CD25⁺ T cells decreased significantly in PBMC of patients with T1D(1.19 ± 0.17% vs 2.78 ± 0.38%, 95% CI:0.87-2.31, P < 0.0001), while expression of Tim4 on CD4⁺CD25⁺ T cells in PBMC was less frequent in patients with T1D than healthy people(3.0 ± 0.39% vs 6.25 ± 1.08%, 95% CI:1.08-5.43, P = 0.0044). The frequencies of CD4⁺CD25⁺Tim1⁺ T cells and CD4⁺CD25⁺Tim4⁺ T cells also decreased in spleen of hyperglycemic NOD mice. There were no significant correlations between CD4⁺CD25⁺Tim1⁺T-cells, CD4⁺CD25⁺Tim4⁺T-cells and any clinical features such as age, HbA1c, Fasting C-peptide, diabetic autoantibodies, disease duration, total cholesterol, LDL, HDL, and TG.

It is the first report of the expression of Tim1 and Tim4 molecules on Treg cells in T1D in the present study. We also presented evidence that the frequencies of Tim1⁺Tregs and Tim4⁺Tregs decreased significantly in both type 1 diabetic patients and hyperglycemic NOD mice. However, the specific functions of Tim1⁺Tregs and Tim4⁺Tregs are still unclear.