Myeloid-derived suppressor cells shift Th17/Treg ratio and promote systemic lupus erythematosus progression through arginase-1/miR-322-5p/TGF-β pathway

Pang, Bo; Yu, Zhen; Hu, Cong; Ma, Zhanchuan; Lin, Shan; Yi, Huanfa

doi:10.1042/cs20200799

Cited by 44 publications

(36 citation statements)

References 34 publications

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“…Myeloid-derived suppressor cells (MDSCs) are immature heterogeneous myeloid-derived cells characterized by immature state and significant ability to suppress the T-cell response. MDSCs significantly expand during inflammation, tumor, and infection, which are comprised of polymorphonuclear (G-MDSCs) and monocytic (M-MDSCs) [ 8 – 10 ]. G-MDSCs are phenotypically and morphologically similar to neutrophils, and M-MDSCs are more similar to monocytes [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

C-type lectin receptor Dectin3 deficiency balances the accumulation and function of FoxO1-mediated LOX-1+ M-MDSCs in relieving lupus-like symptoms

Lü

Kong

et al. 2021

Cell Death Dis

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Recent studies indicate that Toll-like receptors (TLRs) and C-type lectin receptors (CLRs) can function as the signal of pattern recognition receptors, which play a pivotal role in the pathogenesis of the autoimmune disease. Systemic lupus erythematosus (SLE) is a classic autoimmune disease. Previous reports mainly focused on the potential role of TLRs in regulating the development of SLE, but little is known about the role of CLRs in the progression of SLE. Our previous studies showed that the inflammation-mediated accumulation of myeloid-derived suppressor cells (MDSCs) including granulocytic (G-MDSCs) and monocytic (M-MDSCs) participated in the pathogenesis of lupus. Mice deficient in Card9 (the downstream molecule of CLRs) were more susceptible to colitis-associated cancer via promoting the expansion of MDSCs. Whether the abnormal activation of CLRs regulates the expansion of MDSCs to participate in the pathogenesis of lupus remains unknown. In the present study, the expressions of CLRs were examined in both SLE patients and mouse models, revealing the expression of Dectin3 was positively correlated with SLEDAI. Dectin3 deficiency retarded the lupus-like disease by regulating the expansion and function of MDSCs. The mechanistic analysis revealed that Dectin3 deficiency promoted FoxO1-mediated apoptosis of MDSCs. Syk-Akt1-mediated nuclear transfer of FoxO1 increased in Dectin3-deficient MDSCs. Notedly, the accumulation of M-MDSCs mainly decreased in Dectin3−/− lupus mice, and the nuclear transfer of FoxO1 negatively correlated with the expression of LOX-1 on M-MDSCs. The silencing of FoxO1 expression in Dectin3−/− mice promoted the expansion of LOX-1+ M-MDSCs in vivo, and LOX-1+ M-MDSCs increased the differentiation of Th17 cells. Both LOX-1 expression on M-MDSCs and Dectin3 expression on MDSCs increased in patients with SLE. These data indicated that increased LOX-1+ M-MDSCs were related to the exacerbation of SLE development and might be potential target cells for the treatment of SLE.

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Section: Introductionmentioning

confidence: 99%

C-type lectin receptor Dectin3 deficiency balances the accumulation and function of FoxO1-mediated LOX-1+ M-MDSCs in relieving lupus-like symptoms

Lü

Kong

et al. 2021

Cell Death Dis

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“…However, as discussed below, this is not always the case. [105][106][107][108] . Interestingly, patients with SLE showed the accumulation of low-density granulocytes with a high expression of LOX1, a marker of PMN-MDSCs.…”

Section: Enhanced Suppressive Activitymentioning

confidence: 99%

Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity

2021

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Myeloid-derived suppressor cells (MDSCs) are pathologically activated neutrophils and monocytes with potent immunosuppressive activity. They are implicated in the regulation of immune responses in many pathological conditions and are closely associated with poor clinical outcomes in cancer. Recent studies have indicated key distinctions between MDSCs and classical neutrophils and monocytes, and, in this Review, we discuss new data on the major genomic and metabolic characteristics of MDSCs. We explain how these characteristics shape MDSC function and could facilitate therapeutic targeting of these cells, particularly in cancer and in autoimmune diseases. Additionally, we briefly discuss emerging data on MDSC involvement in pregnancy, neonatal biology and COVID-19.

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“…After transplanting of umbilical cord-MSCs, the significantly upregulated levels of FLT3L promoted the proliferation and inhibited the apoptosis of tolerogenic CD1c + DCs, thereby improving the condition of lupus ( 56 ). In SLE, the activity of myeloid-derived suppressor cells impaired in both murine and humans ( 57 ) could promote Th17 cells and Treg differentiation and shift the ratio of Th17/Treg, thereby promoting the progression of SLE ( 58 ). MSC infusion could restore the activity of myeloid-derived suppressor cells in inflammatory and autoimmune diseases, such as Sjögren syndrome ( 28 , 59 ); however, it remains unclear in SLE.…”

Section: Molecular Mechanisms Of Mscs In Slementioning

confidence: 99%

Mesenchymal Stem Cell Therapy: Hope for Patients With Systemic Lupus Erythematosus

Guo

Pan

et al. 2021

Front. Immunol.

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Although previous studies have demonstrated that SLE is related to the imbalance of cells in the immune system, including B cells, T cells, and dendritic cells, etc., the mechanisms underlying SLE pathogenesis remain unclear. Therefore, effective and low side-effect therapies for SLE are lacking. Recently, mesenchymal stem cell (MSC) therapy for autoimmune diseases, particularly SLE, has gained increasing attention. This therapy can improve the signs and symptoms of refractory SLE by promoting the proliferation of Th2 and Treg cells and inhibiting the activity of Th1, Th17, and B cells, etc. However, MSC therapy is also reported ineffective in some patients with SLE, which may be related to MSC- or patient-derived factors. Therefore, the therapeutic effects of MSCs should be further confirmed. This review summarizes the status of MSC therapy in refractory SLE treatment and potential reasons for the ineffectiveness of MSC therapy from three perspectives. We propose various MSC modification methods that may be beneficial in enhancing the immunosuppression of MSCs in SLE. However, their safety and protective effects in patients with SLE still need to be confirmed by further experimental and clinical evidence.

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Myeloid-derived suppressor cells shift Th17/Treg ratio and promote systemic lupus erythematosus progression through arginase-1/miR-322-5p/TGF-β pathway

Cited by 44 publications

References 34 publications

C-type lectin receptor Dectin3 deficiency balances the accumulation and function of FoxO1-mediated LOX-1+ M-MDSCs in relieving lupus-like symptoms

C-type lectin receptor Dectin3 deficiency balances the accumulation and function of FoxO1-mediated LOX-1+ M-MDSCs in relieving lupus-like symptoms

Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity

Mesenchymal Stem Cell Therapy: Hope for Patients With Systemic Lupus Erythematosus

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