Loss of RORγt DNA Binding Activity Inhibits IL-17 Expression in HIV-1 Infected Indian Individuals

Abstract

Abstract IL-17 producing CD4 T cells have recently been shown to play an important role in mucosal immunity in HIV infection. But its role in peripheral immunity and the molecular mechanism underlying its regulation during HIV-1 infection are ill defined. In this study, we report a significant negative correlation between IL-17 production in peripheral blood and HIV-1 plasma viral load (pVL). On further investigation, we observe a marked reduction in retinoid-related orphan nuclear receptor (RORγt; Th17 lineage specific transcription factor) binding at IL-17 promoter in HIV patients with high viremia (pVL>10,000 copies/mL) in contrast to relatively low viremic patients which indicate the magnitude of viral copy number on RORγt binding at IL-17 promoter. Additionally, our study highlights that FoxP3 influences IL-17 production by binding to and acting together with RORγt, consequently inhibiting RORγt binding to IL-17 promoter with growing viremia in HIV infection. Collectively, our data suggest that FoxP3 interacts with RORγt transcription factor in a viral load-dependent fashion and brings about negative impact on IL-17 production in HIV-1 infection.