Dysregulations of follicular helper T cells through IL-21 pathway in age-related macular degeneration

Abstract

Age-related macular degeneration (AMD) is the most common cause of vision loss in the aged population. Aging and inflammation are thought to promote AMD pathogenesis in people with genetic predisposition. Follicular helper T (Tfh) cells play critical roles in inflammatory responses. Here, we investigated circulating Tfh cells in AMD patients. Circulating Tfh cells were defined as CXCR5+ CD4 T cells. Data showed that patients with the wet-type AMD presented significantly higher levels of Tfh cells than non-AMD controls. Interestingly, the Tfh cells from dry and wet AMD patients also presented significantly higher ICOS and PD-1 expression, together with higher IL-17 and IL-21 expression directly ex vivo and following PMA/ionomycin stimulation. The expression of IFNg and IL-10, on the other hand, was not different between Tfh cells from AMD patients and their counterparts in non-AMD controls. Functional analysis revealed that Tfh cells from AMD patients were better at inducing the production of IgG and IgA, and this effect was in an IL-21-dependent manner. Together, we demonstrated that the circulating Tfh cell responses were dysregulated in AMD patients.