Work

Constitutively Active Stat5b Expression in Dendritic Cells Enhances Treg-Mediated Elimination of Autoreactive CD8+ T Cells in Autoimmune Diabetes

Year: 2026

Type: article

Abstract: In type 1 diabetes (T1D) in non-obese diabetic (NOD) mice, dendritic cells (DCs) exhibit a Stat5b mutation that impairs regulatory T cell (Tregs) numbers and suppressive function. To correct this defect, we generated transgenic NOD mice expressing constitutively active Stat5b (NOD.Stat5b-CA) in DCs, which conferred protection from diabetes that was associated with an expanded Treg population and a marked reduction in CD8+ T cell frequencies in secondary lymphoid organs. However, the phenotypic characteristics and underlying mechanisms to eliminate CD8+ T cells in NOD.Stat5b-CA mice are unknown. In this study, we found that the frequency of Tregs was significantly higher in the thymus and peripheral lymphoid organs of NOD.Stat5b-CA mice compared with NOD mice. Tregs in the peripheral lymphoid organs exhibited increased expression of activation markers CD69 and OX40, alongside reduced CD62L. We also found that CD8+ T cell frequencies were reduced in the peripheral organs but not in the thymus of NOD.Stat5b-CA mice, while CD4+ T cell frequencies remained unchanged across all organs. Furthermore, NOD.Stat5b-CA mice exhibited a reduced frequency of central Tregs (CD62Lhigh CD44low) and increased frequency of effector Tregs (CD62Llow CD44high) under steady-state conditions compared to NOD mice. Notably, Tregs from NOD.Stat5b-CA mice displayed enhanced cytotoxic activity, evidenced by increased expression of perforin, granzyme B, and Fas ligand, potentially mediating CD8+ T cell frequency reduction. Collectively, these findings highlight a novel role for Stat5b-CA.DC-educated Tregs in modulating immune responses by eliminating peripheral pathogenic CD8+ T cells via cytotoxic pathways, thereby contributing to immune regulation in NOD.Stat5b-CA mice.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms27020794

Authors: Puregmaa Khongorzul, Farhan Ullah Khan, Daphnée Levasseur, Denis Gris, Abdelaziz Amrani

Institutions: Université de Sherbrooke, Centre Hospitalier Universitaire de Sherbrooke

Language: English

Topic: T-cell and B-cell Immunology

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499