The Th17 Teff population produces pro-inflammatory cytokines IL-17A and IL-17F (Langrish and others 2005) and play an important role in mediating host defenses against bacteria like and as well as (Mignon-Godefroy and others 1995a). a summary of recent research pertaining to the role of cytokines in the pathogenesis of AITD with a particular emphasis on the therapeutic applications of cytokine modulation. Introduction Autoimmune diseases are a group of heterogeneous disorders characterized by abnormal lymphocytic activation directed against self-tissue (Davidson and Diamond 2001; Marrack and others 2001). These diseases occur essentially due to a breakdown in immunological self-tolerance. According to the clonal selection theory (Burnet 1959), self-reactive lymphocytes are deleted at the early developmental stage by negative selection AFX1 and constitute what is called central tolerance. However, it is believed that weakly reactive clones sometimes escape clonal deletion and migrate to the periphery. Physiologically, these potentially self-reactive clones remain either nonresponsive to antigenic stimulation (ignorance) or are rendered anergic (Nossal 1996). In some instances, they undergo activation-induced cell death upon exposure to self-antigen (Green and others 2003). Collectively, these mechanisms of self-tolerance are referred to as cell-intrinsic mechanisms of peripheral tolerance (Schwartz 2005). In recent years, another mechanism of peripheral self-tolerance has been described involving forkhead box P3 (Foxp3) expressing regulatory T cells (Tregs) that actively and dominantly Veliparib dihydrochloride suppress self-reactive T-cells (Sakaguchi and others 2007). This constitutes a cell-extrinsic mechanism of self-tolerance (Schwartz 2005). Autoimmune disease can thus occur when both central and peripheral tolerance mechanisms fail, leading to a pathogenic immune response against a self-antigen. In general, autoimmune diseases can be characterized as T-cell mediated or autoantibody mediated based on the primary effector mechanism and cell type involved in the pathogenesis of the disease. T cell-mediated diseases are characterized by infiltration of T cells into and destruction of the target tissue as seen in Hashimoto’s thyroiditis (HT), type 1 diabetes (T1D) and multiple sclerosis (Crane and Forrester 2005). Autoantibody-mediated diseases are characterized by disruption of function as in Graves’ disease (GD) or destruction of the target tissue as seen in myasthenia gravis, pemphigus vulgaris, systemic lupus erythematosus, rheumatoid arthritis (RA), etc. (Yanaba and others 2008). Autoimmune thyroid diseases (AITD) are the most common organ-specific autoimmune disorders affecting approximately 5% (Caturegli and others 2007) of Veliparib dihydrochloride the overall population. HT and GD are 2 of the most common clinical expressions of thyroid dysfunction but differ in their clinical presentations as well as pathophysiology. HT is a T cell-mediated organ-specific autoimmune disease that results in clinical hypothyroidism due to thyroid destruction and is mediated by infiltrating and/or locally activated thyroglobulin (Tg)-specific T cells. In contrast, GD is characterized by hyperthyroidism due to excessive production of thyroid hormone induced by specific autoantibodies to thyrotropin receptor (TSHR). There is considerable evidence implicating that the actual destruction of thyroid cells in AITD may be caused by different and multiple mechanisms, including auto reactive T-lymphocytes, natural killer (NK) cells, and cytokines. Several studies in animal models have concluded that organ-specific autoimmune thyroiditis (AIT) should be regarded as a polygenic disease that is strongly influenced by environmental factors (Prabhakar and others 2003; Tomer and others 2003; Klecha and others 2008). Although individuals may be genetically predisposed to AIT, the disruption of immune system homeostasis by environmental factors results in thyroid dysfunction. The most significant factor that is likely to be involved in the induction of autoimmunity is a defect or deficiency in the immune regulation, particularly a perturbation in the balance between the effector T cells (Teff) and Tregs that prevent the development of autoimmunity. A murine model of HT called experimental autoimmune thyroiditis (EAT) exhibits key features of HT, including mononuclear cell infiltration that destroy Veliparib dihydrochloride thyroid follicles, presence of autoantibodies, and autoreactive T-cells to thyroid autoantigens (Kong and others 2009). Although this disease is induced by immunization of experimental animals with mouse thyroglobulin (mTg) emulsified in complete Freund’s adjuvant (Vasu and others 2003), it can also be induced with mTg in conjunction with bacterial lipopolysacchharide (LPS) or interleukin (IL)-1 as adjuvant (Esquivel and others 1977; Nabozny and Kong 1992). Antigen presentation in the thyroid draining lymph nodes lead to the differentiation of Tg-specific T-cell subsets that migrate to the thyroid and cause tissue destruction (Fig. 1). This vigorously explored murine model has given us many insights into the molecular mechanisms underlying HT and also enabled us to identify.