Th17 cells in glaucoma patients promote Ig production in IL-17A and IL-21-dependent manner.

Elevated expression of autoantibodies is a hallmark of immune dysregulation in glaucoma and may cause retinal ganglion cell apoptosis and immune-mediated nerve damage, thus contributing to the development of blindness. The cause of autoantibody upregulation remains unclear. Th17 cells are shown to promote autoimmunity and Ig production. Here, we demonstrate that the serum levels of interleukin (IL)-17A and IL-21 are comparable between glaucoma patients and non-glaucoma controls. However, the levels of Th17-promoting cytokines, such as tumour necrosis factor (TNF) IL-6, are higher in glaucoma patients than in controls. Subsequently, we demonstrate that glaucoma patients present upregulated levels of Th17 cells that are quiescent directly ex vivo. Interestingly, compared to the Th17 cells from non-glaucoma subjects, the Th17 cells from glaucoma patients present similar IL-17A production capacity but significantly higher IL-21 production capacity. Given that IL-21 is also described as a specific cytokine of follicular helper T cells, the Ig production by B cells following co-incubation with circulating Th17 cells is investigated. Th17 cells from glaucoma patients present significantly enhanced potential to promote Ig production than the Th17 cells from controls. Both glaucoma patient Th17 cells and control Th17 cells require IL-17A and IL-21 for Ig production. Overall, results from this study suggest that Th17 cells from glaucoma patients present elevated capacity to stimulate Ig production.