The Impact of Zinc on T Cell Motility and the Immunological Synapse

Zinc is an essential trace element with a critical role in regulating immune functions. Patients with autoimmune diseases or chronic lymphatic leukemia often exhibit lower serum zinc levels. As T cells are key mediators of adaptive immunity, disturbances in zinc homeostasis can strongly affect their function. Effective T cell activity depends on directed migration to inflamed tissues, requiring coordinated cytoskeletal reorganization. This process involves the formation of a leading edge and a trailing edge (uropod) and is regulated by the ezrin-radixin-moesin (ERM) complex and its interaction with focal adhesion kinase (FAK). We investigated how zinc availability influences the expression and phosphorylation of FAK and ERM, as well as other migration-related molecules, including LFA-1 and the CD49d/CD44 complex, using Western blot, qRT-PCR, and flow cytometry in the HUT78 T cell line. Cells were cultured in media with different zinc concentrations. Zinc deficiency reduced FAK and ERM expression and decreased LFA-1 while increasing CD49d expression. Overall, these findings indicate that zinc deficiency compromises cytoskeletal remodeling and may impair T cell motility. Maintaining zinc homeostasis could thus enhance T cell migration and strengthen immune responsiveness, highlighting the potential therapeutic relevance of zinc in immune modulation.