CCDC134 ameliorated experimental autoimmune encephalomyelitis by suppressing Th1 and Th17 cells.

CCDC134 (coiled-coil domain containing 134), a cytokine-like molecule, was previously reported to exert antitumor effects by augmenting CD8 T-cell mediated immunity. However, the dynamic changes in CCDC134 expression patterns in the spinal cord that may be involved in the progression of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, remains unclear. In this study, we found that CCDC134 expression was markedly increased in the spinal cord during the progression of EAE. Furthermore, we demonstrated that CCDC134 significantly reduced the severity and slowed the progression of EAE, which correlated with reduced spinal cord inflammation and demyelination. The underlying mechanism of CCDC134-induced effects involved inhibition of T helper (Th)-1 and Th17 cell differentiation and secretion of its key effector molecules IFN-γ and IL-17A via regulation of JAK/STAT signaling. These findings indicate that CCDC134 exerts potent anti-inflammatory effects through the selective modulation of pathogenic Th1 and Th17 cells by targeting critical signaling pathways. The study provides insights into the role of CCDC134 as a unique therapeutic agent for the treatment of autoimmune diseases.