Myeloid-derived suppressor cells contribute to systemic lupus erythaematosus by regulating differentiation of Th17 cells and Tregs

Abstract

Although major advancements have made in investigating the aetiology of SLE (systemic lupus erythaematosus), the role of MDSCs (myeloid-derived suppressor cells) in SLE progression remains confused. Recently, some studies have revealed that MDSCs play an important role in lupus mice. However, the proportion and function of MDSCs in lupus mice and SLE patients are still poorly understood. In the present study, we investigated the proportion and function of MDSCs using different stages of MRL/lpr lupus mice and specimens from SLE patients with different activity. Results showed that splenic granulocytic (G-)MDSCs were significantly expanded by increasing the expression of CCR1 (CC chemokine receptor 1) in diseased MRL/lpr lupus mice and in high-disease-activity SLE patients. However, the proportion of monocytic (M-)MDSCs remains similar in MRL/lpr lupus mice and SLE patients. G-MDSCs produce high levels of ROS (reactive oxygen species) through increasing gp91(phox) expression, and activated TLR2 (Toll-like receptor 2) and AIM2 (absent in melanoma 2) inflammasome in M-MDSCs lead to IL-1β (interleukin 1β) expression in diseased MRL/lpr mice and high-disease-activity SLE patients. Previous study has revealed that MDSCs could alter the plasticity of Th17 (T helper 17) cells and Tregs (regulatory T-cells) via ROS and IL-1β. Co-culture experiments showed that G-MDSCs impaired Treg differentiation via ROS and M-MDSCs promoted Th17 cell polarization by IL-1β in vitro Furthermore, adoptive transfer or antibody depletion of MDSCs in MRL/lpr mice confirmed that MDSCs influenced the imbalance of Tregs and Th17 cells in vivo Our results indicate that MDSCs with the capacity to regulate Th17 cell/Treg balance may be a critical pathogenic factor in SLE.

Neutrophils Slow Disease Progression in Murine Lupus via Modulation of Autoreactive Germinal Centers

“…This same group also described Gr-1+ cell inhibition of Tfh differentiation in vitro and correspondingly increased Tfh with in vivo depletion of Gr-1+ cells, although the specificity of these findings to a neutrophil population is undetermined (46). In other studies, co-culture of neutrophils with T cells impaired Treg differentiation and promoted Th17 differentiation (17), leaving an open question as to whether neutrophils are predominantly immunosuppressive. Additionally, it is unclear to what extent these in vitro assays recapitulate neutrophil-lymphocyte interactions in vivo.…”

Role of innate lymphoid cells in chronic colitis during anti-IL-17A therapy

“…Immune cell plasticity is a distinctive characteristic in adaptive immunity as well as innate immunity. Previous studies have demonstrated that Tregs can be transdifferentiated from Th17 cells by myeloid-derived suppressor cells [26][27][28] . Our results indicate that blocking IL-17A function may also increase the population of RORγt + ILCs (which include LTi cells) via IL-6 production.…”

Increased Levels of Pro-Inflammatory and Anti-Inflammatory Cellular Responses in Parkinson’s Disease Patients: Search for a Disease Indicator

“…It was also reported that MDSCs are responsible for the maturation and transformation of Th17 and T reg cells, and this transformation is highly controlled by cytokines. These findings show that MDSCs can regulate the balance between Th17 and T reg cells to regulate immune balance in the brain [31]. Because administration of an anti-PD drug could alter the expression of Th17 cells [32], the present study assessed newly-diagnosed PD patients without anti-PD drug treatment.…”