Dysregulation of circulating follicular helper T cells in type 2 diabetic patients with diabetic retinopathy

Inflammation is known to be involved in the progression of diabetic retinopathy. Follicular helper T cells (Tfh) play critical roles in the differentiation of long-live plasma cells and production of antibodies, whereas circulating CD4+CXCR5+ T cells may act as a counterpart to measure Tfh cell disorders. In this study, we investigated whether Tfh could be involved in the development of diabetic retinopathy (DR) by assessing circulating Tfh cells in peripheral blood. Data showed that serum levels of total IgG and IgA were both significantly increased in type 2 diabetes mellitus (T2DM) patients with proliferative diabetic retinopathy (PDR) than with non-PDR. Also, B cell activation and differentiation were both enhanced in T2DM patients with PDR. Little changes were detected in levels of Th1, Th2, and Th17 cells. As indicated by elevated serum levels and supernatant from cultured PBMC of IL-21, we found increased circulating Tfh cells in PDR patients with dysregulated subsets. This study suggests the involvement of circulating Tfh cells in DR and, in particular, the pathogenesis of PDR.