Our study complements these findings, further emphasizing the participation of autoimmune mechanisms in the aetiology of the development of TAO, as we show significant
increases of IL-17 and IL-23, cytokines related closely to autoimmunity activation [25–27]. IL-17-producing T cells have been classified as a new effector T cell subset, termed Th17, which is distinct from Th1, Th2 and Treg subsets. There has been much progress in the past year, leading to identification of the molecular mechanisms that drive differentiation of Th17 T cells. This has helped to clarify many aspects of their role in host defence as well as in autoimmunity [28]. Additionally, exactly which cytokines contribute to Th17 formation remains unclear, but TGF-β, IL-6, IL-21 and IL-23 have been implicated in mice and humans [29,30]. It has recently been questioned, however, whether TGF-β is involved at all in humans, and it is assumed that IL-1β may also play a role. Other
Tamoxifen in vivo proteins involved in their differentiation are signal transducer and activator of transcription 3 (STAT3) and the retinoic acid BGB324 research buy receptor-related orphan receptors alpha (ROR-α) and gamma (ROR-γ) [31]. Effector cytokines associated with this cell type are IL-17, IL-21 and IL-22 [32,33]. Th17 cells are implicated in autoimmune disease, and autospecific Th17 cells were shown to be highly disturbing. IL-23 is a member of the IL-12 family of cytokines with proinflammatory properties. Its ability to potently enhance the expansion of Th17 cells indicates responsibility for many of the inflammatory autoimmune responses. Emerging data demonstrate that IL-23 is a key participant in central regulation of the Cobimetinib supplier cellular mechanisms involved in inflammation. Both IL-23 and IL-17 form a new axis through Th17 cells, which has evolved in response to human diseases associated with immunoactivation and immunopathogeny, including bacterial
or viral infections and chronic inflammation. Targeting of IL-23, the IL-23 receptor or the IL-23 axis is a potential therapeutic approach for autoimmune diseases including psoriasis, inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis [27]. In addition to the Th17 profile, autoimmunity development could be defined clearly by monitoring autoantibodies and autoreactive T cells along the time course of TAO. The cytokine environment in peripheral lymphoid tissues and the target organ (vascular) has a strong influence on the outcome of the initial events that trigger autoimmune inflammation. In susceptible individuals, these events drive inflammation and tissue damage in the vascular system. The increased proinflammatory and Th1 results indicate, as in other vasculitis, a contribution to the inflammatory response observed in the vascular levels of smoker patients. The observed increase of Th2 cytokines suggests that an imbalance in the Th1/Th2 cytokine immune response could be related to TAO pathogenesis.