Dysregulated Th17/Treg cell axis is correlated with local and systemic immune response in human intermediate uveitis

Abstract

Th17/Treg cell balance is essential for immune homeostasis and when disrupted, is associated with the occurrence and development of inflammation in numerous autoimmune diseases. However, its contribution in pathophysiology of uveitis remains unexplored. In this study, we deciphered the role of Th17/Treg cell balance in autoimmune uveitis subjects. Using flow cytometry, we detected the frequencies and absolute count of both Th17 and Treg cells in the aqueous humor and peripheral blood of patients and healthy controls. Our results for the first time reveal a significant increase (p < 0.01 and p < 0.005) in Th17 population alongside a significant decrease (p < 0.001 and p < 0.003) in Treg cell population in both the aqueous humor and PBMCs of uveitis patients. Further we analyzed the expression of Th17-Treg associated genes and cytokines via qPCR and ELISA respectively. These findings align with our flow cytometry results, as evident by a significant (p < 0.002) up-regulation of IL-17 and a concurrent down regulation of IL-10 at transcriptional levels. Moreover, IL-17A cytokine was found to be substantially high (p < 0.001) and IL-10 (p < 0.02) down regulated in serum. Interestingly, we demonstrated a significant correlation of Th17/Treg cells in aqueous humor with those in peripheral blood. Conclusively, our results suggest the pivotal role of Th17/Treg cell axis in the immuno-pathophysiology of human uveitis. Further we propose the therapeutic potential of targeting this novel axis for ameliorating the disease burden associated with uveitis.