Altered redox regulation by Nrf2-Keap1 system in dendritic cells of systemic lupus erythematosus patients

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disorder associated with inflammation and multiple organ involvement. Individually, dendritic cells (DCs) and oxidative stress have been well discussed for their critical involvement in the pathogenesis of disease but the precise impact of oxidative stress on DCs in relation to SLE disease activity is yet to be scrutinized. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) pathway is the cellular mechanism to combat increased reactive oxygen species (ROS). The current study was framed in order to understand redox regulation in DCs along with an argument in context to disease activity. Here, 23 SLE patients along with 10 healthy controls were enrolled and disease activity was calculated as the recent change in SLEDAI score. We found the percentage of circulating plasmacytoid DCs (pDCs) was increased with an increase in disease activity. Altered DCs functionality along with disease activity was further supported with the differential concentration of Type I IFNs. The disease activity was positively associated with increased levels of ROS. A relevant reason for increased ROS was further explained with the decreased levels of transcription factor Nrf2. Hence, the present study suggests that SLE specific DCs displayed elevation in ROS and this outcome might be due to impaired free radical clearance by Nrf2. Correlation studies further established an association of disease activity with increased ROS, Type I IFNs levels and decreased activity of oxidative stress regulating enzymes.