Open AccessSwertianolin ameliorates immune dysfunction in sepsis <em>via</em> blocking the immunosuppressive function of myeloid- derived suppressor cells
Author(s) -
Zongfang Ren,
Haoren Tang,
Linjun Wan,
Xing Liu,
Ning Tang,
Lingling Wang,
Zhenhui Guo
Publication year - 2021
Publication title -
european journal of histochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.754
H-Index - 42
eISSN - 2038-8306
pISSN - 1121-760X
DOI - 10.4081/ejh.2021.3292
Subject(s) - myeloid derived suppressor cell , sepsis , immune system , integrin alpha m , spleen , immunology , bone marrow , cancer research , myeloid , medicine , suppressor , cancer
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.