The origin and signaling pathways involved in MDSCs in sepsis. Haematopoietic stem cells (HSCs) differentiate into immature myeloid cells (IMCs) and then quickly differentiate into mature granulocytes, macrophages, or dendritic cells (DCs). In septic conditions, inflammatory factors such as IL-6, IL-10, IL-12, G-CSF, ds RNA, VEGF, and GM-CSF are elevated. They prevent IMCs from differentiating into mature myeloid cells. MDSCs expansion and activation is regulated by many signaling pathways, such as a toll-like receptor (TLR) mediated myeloid differentiation primary response gene 88 (MyD88) signaling and the granulocyte-colony stimulating factor receptor (G-CSFR) mediated the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. They contribute to the increased production of reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS), and arginase 1 (ARG1). MDSCs in sepsis can reduce the capacity of septic monocytes, macrophages, and neutrophils to respond to bacterial toxins, inhibit the activation of T-cells, and promote Th2 polarization. In addition, MDSCs can secrete several cytokines and chemokines, such as interleukin 10, TNF-α, RANTES, and MIP-1β.
