Soh Won-Chang, Park Sang-Moo, Park Jeong-Su, Karabulut Hatice, Kang Hee-Tae, Kang Sun-Kyoung, Kim Min-Sang, Park Jihwan, Lee Sunjae, Kim Hye-Ran, Jun Chang-Duk
Life Sciences and Medical Convergence Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.
Immune Synapse and Cell Therapy Research Center, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.
Proc Natl Acad Sci U S A. 2025 Jul 29;122(30):e2505291122. doi: 10.1073/pnas.2505291122. Epub 2025 Jul 25.
Microvilli on T cells differ from those on epithelial cells, exhibiting filopodia-like characteristics that facilitate the clustering of molecules essential for sensing and cell migration. Recently, they have also been recognized as the structures from which T cell immunological synaptosomes (TIS) are released. In this study, we examined a key determinant of microvilli organization during T cell development and explored the functional roles of these structures, particularly in relation to T cell behaviors. During thymocyte maturation, single-positive thymocytes were found to develop more and longer microvilli than double-positive thymocytes. However, the deletion or inhibition of Cdc42, a small Rho family protein, significantly reduced both the number and length of microvilli in single-positive thymocytes, leading to decreased cell mass. This reduction in microvilli correlates with a decrease in antigen recognition, leading to diminished T cell activation and adhesion, as well as reduced TIS production, while intrinsic migratory properties remain unaffected. These findings highlight the filopodia-like characteristics of T cell microvilli. In this context, Cdc42 contributes significantly to microvilli formation, thereby shaping T cell function.
T细胞上的微绒毛与上皮细胞上的微绒毛不同,具有丝状伪足样特征,有助于聚集传感和细胞迁移所必需的分子。最近,它们也被认为是释放T细胞免疫突触体(TIS)的结构。在本研究中,我们研究了T细胞发育过程中微绒毛组织的一个关键决定因素,并探讨了这些结构的功能作用,特别是与T细胞行为相关的作用。在胸腺细胞成熟过程中,发现单阳性胸腺细胞比双阳性胸腺细胞发育出更多更长的微绒毛。然而,小Rho家族蛋白Cdc42的缺失或抑制显著减少了单阳性胸腺细胞中微绒毛的数量和长度,导致细胞质量下降。微绒毛的这种减少与抗原识别的降低相关,导致T细胞活化和粘附减少,以及TIS产生减少,而内在迁移特性不受影响。这些发现突出了T细胞微绒毛的丝状伪足样特征。在这种情况下,Cdc42对微绒毛形成有显著贡献,从而塑造T细胞功能。