Swertianolin ameliorates immune dysfunction in sepsis via blocking the immunosuppressive function of myeloid-derived suppressor cells

Submitted: 21 June 2021
Accepted: 26 July 2021
Published: 1 September 2021
Abstract Views: 931
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In this study, we studied the long-term proliferation trajectory of myeloid-derived suppressor cells (MDSCs) in murine sepsis model and investigated whether swertianolin could modulate the immunosuppressive function of MDSCs. A murine sepsis model was established by cecal ligation and perforation (CLP), according to the Minimum Quality Threshold in Pre-Clinical Sepsis Studies (MQTiPSS) guidelines. The bone marrow and spleen of the mice were collected at 24 h, 72 h, 7 and 15 d after sepsis induction. The proportions of monocytic-MDSCs (M-MDSCs; CD11b+LY6G-LY6Chi) and granulocytic-MDSCs (G-MDSC, CD11b+ Ly6G+ Ly6Clow) were analyzed by flow cytometry. Then, we have investigated whether swertianolin could modulate the immunosuppressive function of MDSCs in in vitro experiments. G-MDSCs and M-MDSCs increased acutely after sepsis with high levels sustained over a long period of time. G-MDSCs were the main subtype identified in the murine model of sepsis with polymicrobial peritonitis. Furthermore, it was found that swertianolin reduced significantly interleukin-10 (IL-10), nitric oxide (NO), reactive oxygen species (ROS), and arginase production in MDSCs, while reducing MDSC proliferation and promoting MDSC differentiation into dendritic cells. Swertianolin also improved T-cell activity by blocking the immunosuppressive effect of MDSCs. Both subsets of MDSCs significantly increased in the bone marrow and spleen of the mice with sepsis, with G-MDSCs being the main subtype identified. Swertianolin effectively regulated the functions of MDSCs and reduced immune suppression.

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Zongfang Ren, The First School of Clinical Medicine, Southern Medical University, Guangzhou

Department of Medical Intensive Care Unit, General Hospital of Southern Theater Command of PLA, Guangzhou; 
Department of Critical Care Medicine, the Second Affiliated Hospital of Kunming Medical University, Kunming, China

Zhenhui Guo, The First School of Clinical Medicine, Southern Medical University, Guangzhou

Department of Medical Intensive Care Unit, General Hospital of Southern Theater Command of PLA, Guangzhou, China

How to Cite

Ren, Z., Tang, H., Wan, L., Liu, X., Tang, N., Wang, L., & Guo, Z. (2021). Swertianolin ameliorates immune dysfunction in sepsis <em>via</em> blocking the immunosuppressive function of myeloid-derived suppressor cells . European Journal of Histochemistry, 65(3). https://doi.org/10.4081/ejh.2021.3292