Role of regulatory T cells in pathogenesis and therapeutics of Graves’ disease and Graves’ orbitopathy

Graves’ disease (GD) is the most common cause of hyperthyroidism in iodine-replete geographical areas and is ultimately due to autoantibodies (TSHR-Ab) directed to the thyroid-stimulating hormone receptor. Graves’ orbitopathy (GO), the major extrathyroidal manifestation of GD, is an autoinflammatory disease of the orbital tissue, characterized by the expansion of retroorbital fibroblasts and glycosaminoglycans and by extraocular nerve enlargement. Uncertainty still exists over the actors inducing and perpetuating autoimmunity. Regulatory T cells (Tregs) are negative regulators of inflammation and patrol self-tolerance maintenance. Both functional impairment and frequency reduction of Treg are likely in autoimmune disorders. Genome-wide association studies in GD and GO identified polymorphisms of genes involved in Tregs functions, such as CD25 (interleukin 2 receptor), and Forkhead box protein P3. Several studies revealed a reduction in Treg frequency or suppressive actions in these disorders, but their involvement is still an open issue. This book chapter explores the available scientific literature on Tregs in GD and GO.