Myeloid-Derived Suppressor Cells in Autoimmune Disorders

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immature myeloid cells that expand during chronic immune activation. Originally characterised by their capacity to inhibit T-cell responses in cancer, MDSCs have emerged as key modulators in autoimmune settings. Two major subsets—polymorphonuclear (PMN-MDSCs) and monocytic (MO-MDSCs)—exert context-dependent functions that may either attenuate or exacerbate tissue inflammation. Mechanisms include depletion of l-arginine, production of reactive oxygen and nitrogen species, and release of immunoregulatory cytokines such as interleukin-10. Metabolic rewiring, notably enhanced glycolysis, further shapes MDSC phenotypes. Accumulation of MDSCs has been reported in rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, psoriasis and Sjögren’s syndrome. Understanding the balance between their suppressive and pro-inflammatory activities underpins efforts to harness MDSCs as biomarkers or cell-based therapies in autoimmune disorders.

Research from Nature Portfolio

Interleukin-10-expressing MDSCs have been shown to crucially regulate T-cell balance in models of rheumatoid arthritis. Infusion of MDSCs elevated regulatory T-cell frequencies while reducing Th17 and Th1 responses, leading to marked amelioration of joint inflammation. Mechanistic dissection revealed that MDSC-derived interleukin-10 is indispensable for both suppression of pathogenic T-cell proliferation and promotion of FoxP3+ regulatory populations, highlighting these cells as promising therapeutic agents in T-cell-mediated autoimmunity.

Myeloid-Derived Suppressor Cells in Autoimmune Disorders publication trend

The graph below shows the total number of articles in myeloid-derived suppressor cells in autoimmune disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Myeloid-Derived Suppressor Cells (MDSCs): Immature myeloid cells with potent, context-dependent immunoregulatory functions.

Polymorphonuclear MDSCs (PMN-MDSCs): Neutrophil-like subset characterised by rapid induction and reactive oxygen species production.

Monocytic MDSCs (MO-MDSCs): Monocyte-like subset capable of nitric oxide generation and robust cytokine secretion.

Th17 Cells: Pro-inflammatory CD4+ T-cell subset defined by interleukin-17 production, implicated in tissue damage.

Regulatory T Cells (Tregs): CD4+FoxP3+ lymphocytes that maintain tolerance and limit autoimmunity.

References

1. Myeloid-Derived Suppressor Cells: Ductile Targets in Disease. Frontiers in Immunology (2019).
2. Interleukin-10 produced by myeloid-derived suppressor cells is critical for the induction of Tregs and attenuation of rheumatoid inflammation in mice. Scientific Reports (2018).
3. FcγRIIIA activation-mediated up-regulation of glycolysis alters MDSCs modulation in CD4+ T cell subsets of Sjögren syndrome. Cell Death & Disease (2023).
4. The Role of Myeloid-Derived Suppressor Cells in Multiple Sclerosis and Its Animal Model. Aging and Disease (2023).
5. The Influence of Myeloid-Derived Suppressor Cell Expansion in Neuroinflammation and Neurodegenerative Diseases. Cells (2024).