Increased CD14+HLA-DR−/low Myeloid-Derived Suppressor Cells Correlate With Disease Severity in Systemic Lupus Erythematosus Patients in an iNOS-Dependent Manner

Abstract

Myeloid-derived suppressor cells (MDSCs) comprise of a population of cells, which suppress the innate and adaptive immune system via different mechanisms. MDSCs are accumulated under pathological conditions. The present study aimed to clarify the pathological role of MDSCs in systemic lupus erythematosus (SLE) patients. Consequently, the level of circulating M-MDSCs was significantly increased in newly diagnosed SLE patients as compared to healthy controls. An elevated level of M-MDSCs was positively correlated with the disease severity in SLE patients and an immunosuppressive role was exerted in an iNOS-dependent manner. The decrease in the number of M-MDSCs after therapy rendered them as an indicator for the efficacy of treatment. These results demonstrated that M-MDSCs participated in the pathological progress in SLE patients. Thus, MDSCs are attractive biomarkers and therapeutic targets for SLE patients.

Programmed Death-Ligand 1 Expression Potentiates the Immune Modulatory Function Of Myeloid-Derived Suppressor Cells in Systemic Lupus Erythematosus

“…Human total MDSCs (Lin-HLA-DR-CD11b+CD33+ cells), M-MDSC (HLA-DR-CD11b+CD14+ cells) and PMN-MDSC (CD11b+CD14+D15+ cells) were identified as defined previously ( 17 ). As shown in Figures 6A, B , the proportion of total MDSCs and two MDSC subsets were profoundly increased in peripheral blood of lupus patients compared to healthy controls as previously reported ( 7 , 8 ). Interestingly, the mRNA levels of immunoregulatory molecules including PD-L1, arginase-1, and IL-10 were significantly decreased in lupus patients ( Figure 6C ).…”

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“…+CD33+ cells), M-MDSC (HLA-DR-CD11b+CD14+ cells) and PMN-MDSC (CD11b+CD14+D15+ cells) were identified as defined previously (17). As shown in Figures 6A, B, the proportion of total MDSCs and two MDSC subsets were profoundly increased in peripheral blood of lupus patients compared to healthy controls as previously reported (7,8). Interestingly, the mRNA levels of immunoregulatory molecules including PD-L1, arginase-1, and IL-10 were significantly decreased in lupus patients (Figure 6C).…”

“…One report showed that adoptive transfer of monocytic MDSCs shows therapeutic effect in lupus prone mice (5). In contrast, others reported that MDSCs have pathogenic role in lupus (6)(7)(8)(9).…”

Psoriasis and systemic lupus erythematosus in children – literature review based on case report

“…There are both HLA and other genes that predispose to the development of SLE. Lupus erythematosus susceptibility is associated with HLA class II gene polymorphisms, namely HLA-DRB1, -DR3, -DR4, -DR9, -DR11 and -DR15 [24,25]. Other risk factors for SLE include polymorphisms of genes responsible for DNA degradation (TREX, DNase I), type I interferon activation by Toll-like receptors (IRF5/7, STAT4, TLR7/8, IRAK1, ACP5, SPP1), signaling by T lymphocytes (PTPN22, TNFSF4), B lymphocytes (BLK, BANK1) or genes that trigger intracellular signaling pathways (TNFAIP3, TNIP1, PRKCB).…”

“…Other risk factors for SLE include polymorphisms of genes responsible for DNA degradation (TREX, DNase I), type I interferon activation by Toll-like receptors (IRF5/7, STAT4, TLR7/8, IRAK1, ACP5, SPP1), signaling by T lymphocytes (PTPN22, TNFSF4), B lymphocytes (BLK, BANK1) or genes that trigger intracellular signaling pathways (TNFAIP3, TNIP1, PRKCB). In individuals with a genetic predisposition, environmental factors activate autoimmune reactions and lead to the development of inflammation [24,26,27].…”