Long noncoding RNA FOXP1-DT modulates regulatory T cells in Graves' disease.

Regulatory T cells (Tregs) are key contributors to maintaining immune system stability, and their impairment has been linked to the pathogenesis of Graves' disease (GD). However, the precise molecular mechanisms driving Treg dysregulation in GD remain poorly understood. Our previous study identified a dysregulated long noncoding RNA, FOXP1-DT (forkhead box P1 divergent transcript), which might be related to Treg cells. This study aimed to investigate the role of FOXP1-DT in Tregs from individuals with GD. Fifteen patients diagnosed with GD and fifteen age- and sex-matched healthy controls were recruited. Our findings demonstrated that FOXP1-DT expression was markedly decreased in the peripheral blood mononuclear cells of GD patients and exhibited an inverse correlation with the concentration of thyroid-stimulating hormone receptor antibody. FOXP1-DT is mainly located in the nucleus and adjacent to the FOXP1 gene in the genome, a key transcription factor for Treg homeostasis. FOXP1 expression was also significantly reduced in GD patients and correlated positively with FOXP1-DT expression and Treg cell levels. Moreover, silencing FOXP1-DT reduced FOXP1 expression and Treg cell proportion, consistent with the clinical observation of a positive link between decreased FOXP1-DT expression and lower Treg frequency in GD patients. ROC curve analysis showed the potential biomarker value of FOXP1-DT in GD. These findings indicate that downregulated FOXP1-DT may be involved in the process of GD by regulating FOXP1-mediated Treg dyshomeostasis.