Modulation of dendritic cell function and cytokine production to prevent thyroid autoimmunity.
Understanding autoimmune thyroid diseases provides an unique perspective on the role of various components of the immune system in the pathogenesis of organ specific autoimmune diseases, whether the effector mechanism involves autoantibodies or T cells. Hashimoto's thyroiditis (HT) is largely mediated by thyroglobulin specific T cells, while Graves' disease (GD) is mediated by thyrotropin receptor specific autoantibodies. HT is characterized by thyroid destruction mediated by infiltrating or activated resident immune cells through a variety of mechanisms. In contrast GD is characterized by excessive production of thyroid hormone with little or no glandular destruction. Irrespective of the effector mechanism involved, dendritic cells (DCs) are required for the induction of an efficient primary response and thus are the first cells involved in an autoimmune response. DCs also provide the essential link between the innate and the adaptive immune system through co-stimulatory molecules and the production of cytokines and chemokines. Furthermore, inflammatory cytokines also appear to enhance the susceptibility of thyrocytes to apoptosis. In this review, we discuss the role of innate immunity in initiating an adaptive autoimmune response against the thyroid. We will explore the role of different mechanisms involved in breaking self-tolerance to thyroid antigens. Further, we will discuss recent developments in the development of experimental therapeutics against AITD.
Vasu
Chenthamarakshan
C
Department of Surgery, University of Illinois at Chicago, Chicago, IL 60612, USA.
Holterman
Mark J
MJ
Prabhakar
Bellur S
BS
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D006111:Graves Disease / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D007110:Immunity, Active; D007113:Immunity, Innate; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy
D001323:Autoantibodies; D016207:Cytokines