Analysis of autoimmune abnormalities in CD4+T lymphocytes mediated by triiodothyronine in Graves'disease

WANG Lu; ZHANG Haiqing; HE Zhao

doi:10.3969/j.issn.1002-266X.2025.12.006

Abstract：Objective To investigate whether triiodothyronine(T3)is involved in the immune dysregulation mecha-nism of Graves'disease(GD)by modulating CD4+T lymphocytes.Methods Fasting peripheral venous blood was col-lected from 3 GD patients and 6 healthy controls(HCs).CD4+T lymphocytes were isolated and cultured.CD4+T lympho-cytes from 6 HCs were stimulated in vitro with 10 nmol/L T3 for 12 h.Whole-transcriptome RNA sequencing was per-formed on CD4+T lymphocytes from GD patients,unstimulated HCs,and T3-stimulated HCs to screen for differentially ex-pressed genes(DEGs).Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Ge-nomes(KEGG)pathway enrichment analysis were employed to elucidate the biological functions of the identified DEGs.Results A total of 2,449 DEGs(1,797 up-regulated and 652 down-regulated)were identified between GD patients and unstimulated HCs.Compared with unstimulated HCs,T3 stimulation induced 49 DEGs(47 up-regulated and 2 down-regu-lated)in HC-derived CD4+T lymphocytes.The intersection of these two DEG sets yielded 33 overlapping genes,including C5AR1,ITGAX,VEGFA,KLRD1,BTK,PLAUR,and NEU4.GO and KEGG analyses revealed that the signaling path-ways enriched for DEGs in GD patients and T3-stimulated HCs were highly similar,showing significant enrichment in path-ways such as the complement and coagulation cascade,nuclear factor-κB signaling pathway(NF-κB),and autoimmune thyroid disease.Conclusion High levels of T3 may contribute to the immune dysregulation in GD by regulating the ex-pression of genes such as C5AR1,ITGAX,and VEGFA in CD4+T lymphocytes,thereby activating pathways including the complement and coagulation cascade,NF-κB signaling pathway,and autoimmune thyroid disease.