In this study, we firstly demonstrated that inflammatory factor HMGB1 in SLE bone marrow microenvironment could promote the senescence of MSCs via TLR4/NF-κB signaling pathway, and inhibiting HMGB1 by EP could improve lupus nephritis and reverse the senescence signs of MSCs (Figure 7). This evidence concerns the gene TLR4 and systemic lupus erythematosus.