Myeloid-derived suppressor cells contribute to systemic lupus erythematosus by regulating differentiation of Th17 cells and Treg

In this study, we investigated percentage and function of MDSCs using different stages of MRL/lpr lupus mice and specimen from SLE patients with different activity. Result showed that splenic granulocytic (G)-MDSCs were significantly expanded by increasing expression chemokine receptor 1 (CCR1) in diseased MRL/lpr lupus mice and in high active SLE patients. However, percentage of monocytic (M)-MDSCs remains similar in MRL/lpr lupus mice and SLE patients. G-MDSCs produce high levels reactive oxygen species (ROS) through increasing gp91phox expression, and activated Toll-like receptors (TLR) 2 and absent in melanoma (AIM) 2 inflammasome in M-MDSCs lead to IL-1β expression in diseased MRL/lpr mice and high active SLE patients. Previous study revealed MDSCs could construct plasticity of T helper (Th) 17 cells and regulatory T cell (Treg) via ROS and interleukin (IL)-1β. Then the co-culture experiment showed G-MDSCs impaired Treg differentiation via ROS and M-MDSCs promoted Th17 cell polarization by IL-1β in vitro. Furthermore, adoptive transfer or antibody depletion of MDSCs in MRL/lpr mice confirmed MDSCs influenced the imbalance of Treg and Th17 in vivo. Our studies indicate that MDSCs with the capacity to regulate Th17/Treg balance may be a critical pathogenic factor in SLE.

Source: Clinical Science - May 25, 2016 Category: Biomedical Science Authors: Ji, J., Xu, J., Zhao, S., Liu, F., Qi, J., Song, Y., Ren, J., Wang, T., Dou, H., hou, y. Tags: PublishAheadOfPrint Source Type: research