Myeloid-Derived Suppressor Cells in Sepsis: Pathophysiology, Duality, and Therapeutic Frontiers
Shuang Qin1, Zhaofeng Kang2, Qiqi Wu2
1Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract:
Sepsis-induced immunosuppression, one of the factors contributing to mortality, is closely mediated by myeloid-derived suppressor cells (MDSCs). This review first outlines MDSC biology, describing their origin from pathological emergency myelopoiesis and classification into polymorphonuclear and monocytic subsets. We then discuss their dual role: an early, protective modulation of cytokine storm that later evolves into harmful immunosuppression associated with secondary infections and death. The underlying mechanisms involve L-arginine depletion ( via arginase 1/inducible nitric oxide synthase), oxidative stress (reactive oxygen species), and induction of regulatory T cells. Therapeutic strategies are summarized, including interventions targeting MDSC differentiation (e.g., all-trans retinoic acid), metabolism (e.g., fatty acid oxidation inhibitors), precision depletion (e.g., anti-LOX-1), and microbiome modulation. Finally, we address challenges to clinical translation-phenotypic heterogeneity, metabolic ambiguity, and the "double-edged sword" of MDSC targeting. Deeper insights into MDSC biology may help develop strategies to improve outcomes in this severe syndrome.
Insights
Myeloid-Derived Suppressor Cells (MDSCs) drive sepsis-induced immunosuppression and mortality. Understanding MDSC biology and targeting their functions offers potential therapeutic strategies for improving sepsis outcomes.
Area of Science:
- Immunology
- Cell Biology
- Pathophysiology
Background:
- Sepsis mortality is linked to immunosuppression mediated by Myeloid-Derived Suppressor Cells (MDSCs).
- MDSCs originate from emergency myelopoiesis and are classified into polymorphonuclear (PMN-MDSCs) and monocytic (M-MDSCs) subsets.
- MDSCs exhibit a dual role, initially protective against cytokine storm but later causing harmful immunosuppression.
Purpose of the Study:
- To review MDSC biology in sepsis.
- To explore mechanisms of MDSC-mediated immunosuppression.
- To summarize therapeutic strategies and challenges for clinical translation.
Main Methods:
- Literature review of MDSC biology, mechanisms, and therapeutics in sepsis.
- Analysis of MDSC subsets (PMN-MDSCs, M-MDSCs) and their functions.
- Summary of therapeutic interventions targeting MDSC differentiation, metabolism, and depletion.
Main Results:
- MDSC-mediated immunosuppression involves L-arginine depletion, oxidative stress (ROS), and regulatory T cell (Treg) induction.
- Therapeutic strategies include ATRA, FAO inhibitors, anti-LOX-1 antibodies, and microbiome modulation.
- Challenges include MDSC phenotypic heterogeneity and metabolic ambiguity.
Conclusions:
- Targeting MDSC biology presents a promising avenue for sepsis treatment.
- Further research into MDSC mechanisms is crucial for effective clinical translation.
- Addressing the "double-edged sword" nature of MDSC targeting is key for improving sepsis patient outcomes.
