Immunological Drivers in Graves' Disease: NK Cells as a Master Switcher

Graves' disease (GD) is a common autoimmune cause of hyperthyroidism, which is eventually related to the generation of IgG antibodies stimulating the thyrotropin receptor. Clinical manifestations of the disease reflect hyperstimulation of the gland, causing thyrocyte hyperplasia (goiter) and excessive thyroid hormone synthesis (hyperthyroidism). The above clinical manifestations are preceded by still partially unraveled pathogenic actions governed by the induction of aberrant phenotype/functions of immune cells. In this review article we investigated the potential contribution of natural killer (NK) cells, based on literature analysis, to discuss the bidirectional interplay with thyroid hormones (TH) in GD progression. We analyzed cellular and molecular NK-cell associated mechanisms potentially impacting on GD, in a view of identification of the main NK-cell subset with highest immunoregulatory role. The autoimmune thyroid disorder, known as Graves' disease (GD), is the most frequent cause of hyperthyroidism in iodine sufficient areas (1). Production of autoantibodies against the TSH-receptor (TRAb) represents the ultimate step for disease progression (2). Therefore, identification of the major drivers involved in triggering and progression of the disease, still represents an unmet need (1). There is a large consensus that identification of all potential factors involved in the pathogenesis of GD might favor the development of a more efficient treatment strategy, as well as of prevention approaches (3). This would be of paramount importance in view of the current lack of an effective pharmacological therapy for GD (4–6). Natural killer (NK) cells, whose has been initially defined in virus clearance and defense against tumors, represent a highly heterogenous cell population. More recently, they have been shown to be involved in autoimmune disorders with both pathogenic and regulatory roles (7). While it is widely accepted that abnormalities in the adaptive immune response underpin autoreactivity and autoimmune diseases, it is also clear that other effector cells within the innate immunity compartment can act as relevant players. The major aim of this narrative review was to discuss the potential involvement of NK cells in the pathogenesis of Graves' disease and to speculate on potential future treatment/prevention strategies, based on NK cells as a target and/or as a tool for therapy

Graves' disease (GD) is a common autoimmune cause of hyperthyroidism, which is eventually related to the generation of IgG antibodies stimulating the thyrotropin receptor. Clinical manifestations of the disease reflect hyperstimulation of the gland, causing thyrocyte hyperplasia (goiter) and excessive thyroid hormone synthesis (hyperthyroidism). The above clinical manifestations are preceded by still partially unraveled pathogenic actions governed by the induction of aberrant phenotype/functions of immune cells. In this review article we investigated the potential contribution of natural killer (NK) cells, based on literature analysis, to discuss the bidirectional interplay with thyroid hormones (TH) in GD progression. We analyzed cellular and molecular NK-cell associated mechanisms potentially impacting on GD, in a view of identification of the main NK-cell subset with highest immunoregulatory role.