CD8+iTregs attenuate glomerular endothelial cell injury in lupus-prone mice through blocking the activation of p38 MAPK and NF-κB.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease. Endothelial cell injury plays an important role in the inflammatory processes associated with SLE. CD4+Foxp3+regulatory T cells (Tregs) reduce the injury to endothelial cells induced by inflammatory factors. As a newly identified regulatory T cell, we previously reported that CD8+CD103+iTregs had similar effects to those of CD4+iTregs in the process of immunoregulation. In this paper, we further explored the effect and mechanism of CD8+iTregs on endothelial cell injury. The expressions of vascular cellular adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) in MRL/lpr mouse glomerular endothelial cells (lupus-MGECs) were estimated by quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay and Western blotting. The lupus-MGEC apoptosis rate was detected by flow cytometry and the adhesion of monocyte-like cells to lupus-MGECs exposed to lipopolysaccharide (LPS) was determined by the adhesion assay. Additionally, the expressions of P-p38, P-NF-κB and P-IκBα were detected by Western blotting. The results showed that LPS increased the expressions of VCAM-1, ICAM-1, IFN-γ, TNF-α, IL-6 and MCP-1 in lupus-MGECs, while CD8+iTregs significantly decreased the levels of these adhesion molecules and inflammatory mediators. Furthermore, CD8+iTregs alleviated lupus-MGEC apoptosis and inhibited the adhesion of monocyte-like cells to lupus-MGECs. Both nuclear factor-κB (NF-κB) and p38 mitogen-activated protein kinase (MAPK), activated by LPS, were suppressed by CD8+iTregs. These findings suggest that CD8+iTregs attenuate LPS-induced glomerular endothelial cell injury through blocking the activation of p38 MAPK and NF-κB in lupus-MGECs. The protective effect of CD8+iTregs indicates their possible therapeutic application in Lupus nephritis.