Malat1 regulates PMN-MDSC expansion and immunosuppression through p-STAT3 ubiquitination in sepsis
Yaodong Wang, Caiyan Zhang, Tingyan Liu, Zhenhao Yu, Kexin Wang, Jiayun Ying, Yao Wang, Ting Zhu, Jingjing Li, Xiuchuan Lucas Hu, Yufeng Zhou, Guoping Lü
Abstract
, Malat1 down-regulation increases the proportion of PMN-MDSCs and enhanced its immunosuppressive ability. Mechanistically, Malat1 limits the differentiation of PMN-MDSCs by accelerating the degradation of phosphorylated STAT3. Furthermore, Stattic, an inhibitor of STAT3 phosphorylation, improves the survival of septic mice by inhibiting PMN-MDSCs. Overall, the study identifies a novel insight into the mechanism of sepsis-induced MDSCs and provides more evidence for targeting MDSCs in the treatment of sepsis.
Topics & Concepts
SepsisMALAT1ImmunosuppressionMyeloid-derived Suppressor CellImmunologyCancer researchBiologyMedicineSuppressorDownregulation and upregulationCancerGeneInternal medicineLong non-coding RNABiochemistryImmune cells in cancerImmune Response and InflammationInflammation biomarkers and pathways