Cytokines that Modulate the Differentiation of Th17 Cells in Autoimmune Uveitis

Abstract

Increasing evidence has suggested that T helper 17 (Th17) cells play a central role in the pathogenesis of ocular immune disease. The association between pathogenic Th17 cells and the development of uveitis has been confirmed in experimental and clinical studies. Several cytokines affect the initiation and stabilization of the differentiation of Th17 cells. Therefore, understanding the mechanism of related cytokines in the differentiation of Th17 cells is important for exploring the pathogenesis and the potential therapeutic targets of uveitis. This article briefly describes the structures, mechanisms, and targeted drugs of cytokines—including interleukin (IL)-6, transforming growth factor-β1 (TGF-β1), IL-1β, IL-23, IL-27, IL-35, IL-2, IL-4, IL-21, and interferon (IFN)-γ—which have an important influence on the differentiation of Th17 cells and discusses their potential as therapeutic targets for treating autoimmune uveitis.

Therapeutic Potential of d-MAPPS™ for Ocular Inflammatory Diseases and Regeneration of Injured Corneal and Retinal Tissue

“…CD4 + Th1 cells, in an IFN-γ-dependent manner, induce the activation of inflammatory M1 macrophages which, through the release of NO and ROS, aggravate acute uveitis [ 22 , 23 ]. CD4 + Th17 cells produce IL-17 and IL-22, which activate N1 neutrophils and innate lymphoid cells, playing important roles in the development and progression of chronic uveitis [ 24 ].…”

Autoreactive lymphocytes in multiple sclerosis: Pathogenesis and treatment target

“…Similar to IL-10, IL-35 has strong anti-inflammatory activity by inhibiting differentiation of pathogenic Th1 and Th17 as well as promoting development of Bregs and Tregs (209,210). In addition to IL-10 and IL-35, Bregs could secrete TGF-b, thus, suppressing Th1 proliferation while promoting Treg cells differentiation (211). The role of Bregs in pathogenesis of MS was demonstrated in a study, where the reduction of the naïve/memory Bregs was found during a relapse (212).…”

Histone deacetylase 1 and 3 inhibitors alleviate colon inflammation by inhibiting Th17 cell differentiation

“…The differentiation of T helper 17 (Th17) cells is induced by a combination of transforming growth factor‐β (TGF‐β) and interleukin (IL)‐6. Inflammatory factors (such as IL‐1βand IL‐23) secreted by activated dendritic cells and macrophages residing in the laminae of the intestine can further promote the differentiation of Th17 cells 6,7 . Activated Th17 cells secrete various cytokines, of which IL‐17A plays a major pro‐inflammatory role 8 .…”

“…Inflammatory factors (such as IL-1βand IL-23) secreted by activated dendritic cells and macrophages residing in the laminae of the intestine can further promote the differentiation of Th17 cells. 6,7 Activated Th17 cells secrete various cytokines, of which IL-17A plays a major pro-inflammatory role. 8 Numerous studies have shown a close association between IBD and Th17 cell levels.…”