The crosstalk between SPP1+ macrophages and follicular helper T cells promotes the immune disorder of Graves' disease

Graves' disease (GD) is an organ-specific autoimmune condition involving intricate interactions among various components of thyroid tissue. In this study, we employed single-cell and spatial transcriptomics to characterize immune cells and spatial gene expression patterns in thyroid tissues and to identify phenotypic alterations in control individuals, patients with GD, and patients in remission. We found that the proportion of SPP1 + macrophages was increased in the thyroid tissues of patients with GD, characterized by the transcriptional profiles of SPP1 , APOE , and APOC1 . SPP1 + macrophages may engage in crosstalk with CXCL13 + Tfh cells through mechanisms such as SPP1-CD44 interactions, potentially exacerbating immune microenvironment dysregulation. In addition, abundant newly formed vascular endothelial cells were observed. SPP1 + macrophages may promote this process through the SPP1 and VEGF signaling pathways. Therefore, therapeutic modulation of this subgroup may represent a promising strategy for GD.