Circulating CD14+HLA-DR-/low Myeloid-Derived Suppressor Cells as Potential Biomarkers for the Identification of Psoriasis TCM Blood-Heat Syndrome and Blood-Stasis Syndrome

Abstract

Psoriasis is a chronic autoimmune disease. Identification of the biomarkers responsible for Traditional Chinese Medicine (TCM) syndromes of psoriasis can help researchers recognize the different aspects of psoriasis and find novel therapeutic targets for the treatment of psoriasis. The current study investigated the levels of circulating Mo-MDSCs and Mo-MDSC-associated immune factors in the peripheral blood of psoriasis patients with different TCM syndromes. We found that the frequency of Mo-MDSCs (CD14⁺HLA-DR^-/low cells) among CD14⁺ cells from plaque psoriasis patients with blood-stasis (BS) syndrome was significantly increased when compared with healthy controls (p < 0.001) and blood-heat (BH) syndrome group (p < 0.001), respectively. However, serum IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, IFN-γ, iNOS, Arg-1, and NO concentration showed no statistically significant difference between healthy controls and psoriasis patients as well as no significant difference between the BH and BS syndrome groups. Compared with healthy controls, the mRNA expression of Arg-1, TNF-α, ROR-γ, and PD-L1 was increased, while the mRNA expression of PD-1 and IL-10 was decreased in PBMCs from psoriasis patients. Moreover, the mRNA expression of TNF-α and FOXP3 in PBMCs showed a pronounced statistical difference between the psoriatic BH syndrome group and the BS syndrome group. Therefore, we provide evidence that the percentage of CD14⁺HLA-DR^-/low MDSC/ CD14⁺ cells and TNF-α and Foxp3 mRNA expression levels in PBMCs are potential biomarkers for distinguishing TCM BH syndrome and BS syndrome.

Figure 1

Frequency of circulating Mo-MDSCs is increased in the peripheral blood of patients with psoriasis with BS syndrome. Representative flow cytometry panels show quantification of Mo-MDSCs among PBMCs of healthy control subjects (a), psoriatic BS syndrome group (b), and psoriatic BH syndrome group (c). (d) The frequency of HLA-DR^−/low cells among CD14⁺ cells from psoriatic BS syndrome is significantly higher when compared to healthy controls or the psoriatic BH syndrome group, respectively (^∗∗∗∗p < 0.0001). (e) The frequency of HLA-DR^−/low cells among CD14⁺ cells of psoriasis patients is higher when compared to healthy controls.

Figure 2

Correlation analyses of psoriasis severity as assessed by the psoriasis area and severity index (PASI) and the percentage of circulating Mo-MDSCs among CD14⁺ monocytes. (a) PASI and percentage of circulating Mo-MDSCs among CD14⁺ monocytes in the BH group (n = 20); (b) PASI and percentage of circulating Mo-MDSCs among CD14⁺ monocytes in the BS group (n = 22); (c) PASI and percentage of circulating Mo-MDSCs among CD14⁺ monocytes in all psoriasis patients.

Figure 3

Detection of serum immune factor levels in psoriasis patients and healthy controls.

Figure 4

Detection of Mo-MDSC-associated immune factor mRNA in PBMCs. (a) mRNA levels of Arg-1, iNOS, IL-23, TNF-α, FOXP3, PD-1, PD-L1, and IL-10 in PBMCs from the HC and PP groups; (b) ROR-γ mRNA levels in PBMCs of the HC and PP groups; (c) mRNA levels of Arg-1, iNOS, TNF-α, Foxp3, PD-1, PD-L1, and IL-10 in PBMCs of the HC, BS, and BH groups; (d) ROR-γ mRNA levels in PBMC from the HC, BS, and BH groups (^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001, ^∗∗∗∗p < 0.0001).