Identification and Experimental Validation of Genes Associated with Programmed Cell Death in Dendritic Cells of the Thyroid Tissue in Hashimoto's Thyroiditis

Abstract

Abstract Introduction: Hashimoto's thyroiditis (HT) is a chronic autoimmune disorder. Being antigen-presenting cells, dendritic cells induce various types of programmed cell death (PCD), resulting in immune disorders. This study aimed to identify genes associated with various PCD pathways in dendritic cells within the thyroid tissue of HT patients. Methods We downloaded the single-cell RNA-sequencing dataset HRA001684 from the National Genomics Data Center (NGDC) database to calculate the area under the curve (AUC) scores for PCD-related genes. We obtained the mRNA sequencing datasets GSE138198 and HRA001684 from Gene Expression Omnibus and NGDC, respectively. Differentially expressed genes (DEGs) were identified by comparing the normal and HT groups in GSE138198 and HRA001684. The intersection of these DEGs with PCD-related genes led to the identification of 17 PCDDEGs. Results The AUC scores showed that dendritic cells exhibited significantly high levels of necroptosis, ferroptosis, pyroptosis, autophagy, and PANoptosis and expressed six PCDDEGs: TNFAIP3, CYBB, PTPN6, STAT1, TGFB1, and NLRP3. These genes displayed an AUC > 0.8 for HT in the GSE29315, GSE138198, and HRA001684 datasets and clinical thyroid samples, confirming their diagnostic accuracy. Moreover, their expression was positively correlated with the serum levels of thyroid peroxidase and thyroglobulin antibodies. Finally, all PCDDEGs were inversely associated with thyroid follicular epithelial cells. Discussion These findings suggest that dendritic cells play a crucial role in mediating PCD within the thyroid tissues of HT patients. Moreover, TNFAIP3, CYBB, PTPN6, STAT1, TGFB1, and NLRP3 may crucially contribute to the pathogenesis of HT through PCD pathways.