Cdc42 defect reveals a role for microvilli in T-cell immunity 2400

Abstract Description Microvilli on T cells exhibit filopodia-like structures that support molecule clustering, essential for migration and immune response. Despite their importance, how these structures are organized during T-cell development remains unclear, and their functions are still not fully understood. Given Cdc42’s established role in filopodia formation, we examined its impact on microvilli development and broader T cell functions. Electron microscopy revealed that single-positive thymocytes have more and longer microvilli than double-positive thymocytes. Knocking out Cdc42 significantly reduced microvilli length and number in single-positive thymocytes, leading to decreased cell mass and downregulation of TCR, CD3, and L-selectin. These changes impaired T-cell adhesion to high-endothelial venules and weakened antigen recognition, thereby reducing T-cell activation, while intrinsic migratory properties remained unaffected. Additionally, the generation of TCR+ microvilli particles was reduced, leading to diminished proliferation. These findings highlight Cdc42’s critical role in microvilli assembly, which in turn affects subsequent T-cell functions. Funding Sources This work was supported by 2015R1A3A2066253, RS-2024-00419699, RS-2024-00341869, and NRF-2020M3A9G3080281 through National Research Foundation (NRF) grants funded by the Ministry of Science and ICT (MSIT), Korea. 2022R1A2C4002627 through National Research Foundation (NRF) grants funded by the Ministry of Education (MOE), Korea. Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)