| First Author | Zhang T | Year | 2023 |
| Journal | Front Immunol | Volume | 14 |
| Pages | 1133111 | PubMed ID | 37234153 |
| Mgi Jnum | J:346306 | Mgi Id | MGI:7484944 |
| Doi | 10.3389/fimmu.2023.1133111 | Citation | Zhang T, et al. (2023) CCDC134 facilitates T cell activation through the regulation of early T cell receptor signaling. Front Immunol 14:1133111 |
| abstractText | Modulation of surface T cell antigen receptor (TCR) expression is crucial for proper T cell development and maintenance of mature T cell function at steady state and upon stimulation. We previously determined that CCDC134 (coiled-coil domain containing 134), a cytokine-like molecule that served as a potential member of the gammac cytokine family, contributes to antitumor responses by augmenting CD8(+) T cell-mediated immunity. Here we show that T cell-specific deletion of Ccdc134 decreased peripheral mature CD4(+) and CD8(+) T cells, which resulted in impaired T cell homeostasis. Moreover, Ccdc134-deficient T cells exhibited an attenuated response to TCR stimulation in vitro, showing lower activation and proliferative capacity. This was further reflected in vivo, rendering mice refractory to T cell-mediated inflammatory and antitumor responses. More importantly, CCDC134 is associated with TCR signaling components, including CD3, and attenuated TCR signaling in Ccdc134-deficient T cells via altered CD3 ubiquitination and degradation. Taken together, these findings suggest a role for CCDC134 as a positive regulator of TCR-proximal signaling and provide insight into the cell-intrinsic functional consequences of Ccdc134 deficiency in the attenuation of T cell-mediated inflammatory and antitumor responses. |
