Follicular helper T cells in Graves' disease: pathogenic mechanisms and therapeutic implications

Graves' disease (GD) is a specific autoimmune disorder that primarily affects the thyroid gland, leading to thyrotoxicosis and potentially accompanied by extrathyroidal manifestations such as Graves' ophthalmopathy and pretibial myxedema. Its pathogenesis involves the abnormal proliferation of autoreactive B cells, which subsequently produce autoantibodies targeting the thyroid-stimulating hormone receptor (TSHR), resulting in excessive secretion of thyroid hormones. Helper T cells (Th cells) play a significant role in this process. In recent years, follicular helper T cells (Tfh cells) have been identified as a novel subset of Th cells, primarily residing in the germinal centers (GCs) of lymphoid organs and in peripheral blood. Tfh cells facilitate B cell development and antibody production, thus playing a crucial role in the pathogenesis of GD. Their aberrant proliferation and function may lead to the production of autoantibodies and pathological processes such as tissue damage. This review summarizes the latest advancements in the biology of Tfh cells and their role in GD, exploring their potential as therapeutic targets, thereby providing new insights into the pathogenesis and treatment of GD.