Immune regulation and therapeutic targets in sepsis: insights from single-cell transcriptomics

Sepsis is a life-threatening systemic inflammatory syndrome often associated with immune dysregulation, multi-organ dysfunction, and high mortality. In recent years, single-cell transcriptomics has generated a wealth of data on immune cell heterogeneity, lineage reprogramming, and functional states in sepsis. However, a systematic integration and summary of immune cell subsets and regulatory mechanisms are still lacking, limiting a comprehensive understanding of dynamic immune responses and potential therapeutic targets across disease progression. This review synthesizes advances from single-cell and multi-omics studies in sepsis, highlighting myeloid-biased hematopoietic stem/progenitor cell differentiation and emergency granulopoiesis, immunosuppressive features of neutrophils and MDSCs, T/NK cell exhaustion and metabolic adaptation, B cell and plasma cell reprogramming, and glial cell polarization affecting the blood-brain barrier. Key molecular mechanisms, including TLR4 acetylation, STAT3-CEBPB axis, Fu-Hp/Mincle signaling, Treg metabolism, and the kynurenine pathway, are discussed, alongside potential biomarkers and therapeutic targets such as inflammatory CD16⁺ monocytes, SRS1 neutrophils, PICS-associated T/B cells, and polarized glial cells. This integrated perspective provides a framework for understanding systemic and central immune regulation in sepsis, underscores the importance of dynamic, multi-omics, and spatial analyses, and establishes a foundation for early diagnosis, prognosis evaluation, and precision immunotherapy.