TABLE 1.
Markers of immune cells that can be used for diagnosis and/or treatment in DW.
| Immune cells | Differentiation markers | Diagnosis and/or treatment |
|---|---|---|
| T Cells | Effector T-cells↑ | The accumulation of effector T-cells is the core of DFU, diminish T-cells activation and tissue accumulation may accelerate DW healing Moura et al. (2017) |
| Memory T-cells↑ | ||
| Naive T-cells↓ | ||
| B Cells | BAFF↑ | The BAFF levels were superior to that of CRP levels in diagnosing DFUDhamodharan et al. (2019) |
| Neutrophils (PMNs). | NETs↑ | PAD4 inhibition and cleavage of NETs by dnaseⅠmay improve DW healing Wong et al. (2015) |
| PAD4, H3Cit↑ | ||
| NET-specific markers | NET-specific markers H3Cit negatively correlated with wound healing in DFU patients Yang et al. (2020) | |
| H3Cit↑ | ||
| C5a↑ | Inhibitor of complement C1 ( PIC1). may reduce the infiltration of PMNS and improve DW healing Cunnion et al. (2017) | |
| C3-fragment deposition↑ | ||
| Monocytes/Macrophages (Mo/Mp). | Proportions of bone MyP↑circulating Ly6CHi Mo↑ | Myeloid lineage commitment in BM may contribute to increased mp numbers observed in DW strategies to regulate monopoiesis during homeostasis or post wounding may improve DW healing Barman et al. (2019) |
| Spleen Ly6CHi Mo↑ | ||
| HSPC response↑ | ||
| MPP2, MMP-3↓ | ||
| The influx of Ly6CHi Mo↑ | Time-dependent control of Mo/Mp influx after an injury such as anti-mcp-1 antibody may represent a novel therapeutic target for impaired DW healing Kimball et al. (2018) | |
| Maturation to Ly6CLo Mo↓ | ||
| IL-1β, MMP-9, TNF-α↑ | Inhibiting IL-1β downregulate proinflammatory mp and upregulate prohealing mp in DW which may improve DW healing Mirza et al. (2013) | |
| CD206, IGF-1↓ | ||
| TGF-β, il-10↓ | ||
| CD68, iNOS, TNF-α, IFN-γ↑ | Blocking the AGE-RAGE interaction may improve the function of Mp Wang Q. et al. (2017) | |
| CD206, PDGF↓ | ||
| Jmjd3, IL-12↑ | Histone demethylase inhibitor such as GSK-J4 may improve chronic inflammation and DW healing Gallagher et al. (2015) | |
| H3K27me3↓ | ||
| UA, XO↑ | IFNβ may be an attractive therapeutic target and XO inhibitors such as allopurinol may reduce the production of IL-1β and improve DW healing Kimball et al. (2019) | |
| Setdb2, H3K9me3↓ | ||
| IFNβ↓ | ||
| Mp senescence↑ | CXCR2 antagonist treatment such as SB265610 reduces inflammation Immune-aging and improve DW healing Wilkinson et al. (2019) | |
| CXCR2↑ | ||
| SASP↑ |
Partial Abbreviations: BAFF: B-cell activating factor, PAD4: Peptidylarginine deiminase 4 (encoded by Padi4 in mice)., H3Cit: Citrullinated histone H3, NETs: Neutrophil extracellular traps, BM: Bone marrow, HSPC: Hematopoietic stem and progenitor cell, MyP: Marrow myeloid progenitors, MPP: Multipotent progenitor, Ly6CHi: CX3CR1lowCCR2+Ly6C+, Ly6CLo: CX3CR1highCCR2-Ly6C−, IL-1β: Interleukin-1β, TNF-α: Tumor necrosis factor-α, MMP-9: Matrix metalloprotein-9, IL-10: Interleukin-10, TGF-β: Transforming growth factor-β, IGF-1: Insulin-like growth factor-1, AGEs: Advanced glycation end products, PDGF: Platelet derived growth factor, Jmjd3: JumanjiC (JmjC) domain-containing protein, UA: Uric acid, XO: Xanthine oxidase, SASP: Senescence-associated secretory phenotype.