The role of Tim-3+T cell subsets in the peripheral blood of patients with COVID-19 and diabetes

Corona Virus Disease 2019 (COVID-19) and diabetes interact to influence disease severity, yet their combined immunological characteristics remain unclear. Here, we analyzed Tim-3+ T cells in patients with COVID-19, Type 1 Diabetes (T1D), or both conditions. COVID-19 reduced peripheral T cell subsets but increased Tim-3+ cells, while T1D and COVID-19 with T1D showed the opposite pattern. Patients with Type 2 Diabetes (T2D) exhibited no significant alterations. In human samples and mouse models, Tim-3+ T cells demonstrated impaired activation and cytokine production. RNA-seq analysis in mice and RT-PCR analysis in human samples together identified the dysregulation of the JAK-STAT pathway in Tim-3+ T cells. These findings highlight Tim-3-mediated JAK-STAT dysregulation in T-cells as a potential mechanism linking COVID-19 and T1D, offering insights for therapeutic targeting.