Study on the effect of HMGB1 on immune cells isolated from SLE mice

Abstract

Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and its pathogenesis is related to the balance and dysfunction of dendritic cells (DCs). The therapy targeting dendritic cells has become an important means to treat SLE and autoimmune diseases. Besides, HMGB1 is highly expressed in the serum of patients with SLE. Therefore, this study intended to find the function of HMGB1 on immune cells in SLE. We used the MRL/lpr mice as SLE model animals, then we isolated the peripheral blood of SLE mice to obtain CD14⁺ cells, which was induced into monocyte-derived Dendritic cells (Mo-DCs). We also obtained CD14⁺ cells from peripheral blood to explore the effect of HMGB1 treated Mo-DCs. Then followed the HMGB1 treatment, flow cytometry, ELISA, WB and CCK8 assay. The results showed that HMGB1 can stimulate the maturation of DCs, and activated mTOR pathway, and affect the proliferation and differentiation of CD4⁺ cells. What's more, HMGB1 seemed to enter cells through the endocytosis of Toll-like receptor, and its function maybe related to endoplasmic reticulum stress. The further research found tunicamycin (endoplasmic reticulum stress inducer) and rapamycin (mTOR inhibitor) can inhibit the activation of Mo-DCs. Therefore, we thought that HMGB1 enters DCs by TLR6 and regulate the activation of DCs and the differentiation of CD4⁺ cells by influencing endoplasmic reticulum stress and the mTOR pathway.