Regulation of Th1 and Th17 cell differentiation in uveitis

Abstract

Noninfectious uveitis is one of the sight-threatening disorders that are associated with sys-temic autoimmune diseases, such as Behçet's disease. Uveitis is often recurrent and causes subsequent tissue destruction and scarring, especially in the retina and uvea, leading to permanent loss of vision. Early studies have shown that T-helper (Th) 1 cells are the major effector cells and are critical for the development of uveitis. Recently, Th17 cells, a newly defined effec-tor T-helper lineage that is distinct from Th1 and Th2 cell lineages, were also shown to play a pivotal role in the pathogenesis of uveitis. Furthermore, several clinical studies have reported that biological agents targeting Th17-related cytokines, such as IL-6, IL-23, and TNF-, induced and maintained remission in human autoimmune diseases, including rheumatoid arthritis, Crohn's disease, psoriasis, and noninfectious uveitis. In this mini-review, we focus on the roles of proinflammatory cytokines in the regulation of Th1 and Th17 cell responses in uveitis, both experimentally and clinically. A deeper understanding of the underlying mechanisms will provide new insights into the development of new therapies for refractory human noninfectious uveitis.