The Immunoregulatory Role of Myeloid-Derived Suppressor Cells in the Pathogenesis of Rheumatoid Arthritis

Abstract

Myeloid-derived suppressor cells (MDSCs) are a group of cells that regulate the immune response and exert immunosuppressive effects on various immune cells. Current studies indicate that MDSCs have both anti-inflammatory effects and proinflammatory effects on rheumatoid arthritis (RA) and RA animal models. MDSCs inhibit CD4 + T cells, which secrete proinflammatory factors such as IFN-γ, IL-2, IL-6, IL-17, and TNF-α, by inhibiting iNOS, ROS, and IFN-γ and promoting the production of the anti-inflammatory factor IL-10. MDSCs can suppress dendritic cells by reducing MHC-II and CD86 expression, expand Treg cells in vitro through the action of IL-10, inhibit B cells through NO and PGE 2, and promote Th17 cell responses by secreting IL-1β. As a type of osteoclast precursor cell, MDSCs can differentiate into osteoclasts through activation of the NF-κB pathway via IL-1α. Overall, our study reviews the research progress related to MDSCs in RA, focusing on the effects of MDSCs on various types of cells and aiming to provide ideas to help reveal the important role of MDSCs in RA.

Identification of Diagnostic Signatures and Immune Cell Infiltration Characteristics in Rheumatoid Arthritis by Integrating Bioinformatic Analysis and Machine-Learning Strategies

“…It is well known that B cells are a vital part pertaining to human adaptive immunity, whereas these cells under RA become a possible factor in RA pathogenesis (40). Local synthesizing process for cytokine (e.g., IL-1a, IL-23, IL-12, IL-6, and TNF-a) under the induction from local autoreactive B cell was suggested to impact pathologyassociated RA cells, triggering bone injury, inflammation, and immune disorder (41,42). It is currently evidenced that CD4+ T helper cells impact the pathogenesis of RA largely via the secreting process for cytokine and chemokine.…”

Inhibition of Histone H3 Lysine-27 Demethylase Activity Relieves Rheumatoid Arthritis Symptoms via Repression of IL6 Transcription in Macrophages

“…Moreover, systemically decreased levels of IL6 and TNFa were also observed in peripheral blood (Figure S1). As altered IL17 and IL10 levels were observed, which are crucial in Th17 and Treg differentiation and Th17 and Treg were reported to play indispensable roles in RA (42)(43)(44), the abundance of CD4 +IL17+ and CD4+ CD25+FOXP3+ cells in mice inguinal lymph node was evaluated by flow cytometry. The ratio of Treg/Th17 has been used to characterize the severity of RA (45,46), and our results showed that GSK-J4 could downregulate the ratio of Treg/Th17 (Figure S2), further suggesting that inhibition of demethylase activity could be beneficial to CIA, at least in the experimental RA mice model.…”

A high percentage of CD16+ monocytes correlates with the extent of bone erosion in Chronic Lymphocytic Leukemia patients: the impact of leukemic B cells in monocytes differentiation and osteoclasts maturation.

“…It is of further note that, in a particular context, Myeloid-Derived Suppressor Cells (MDSCs), may differentiate towards osteoclasts precursors, [44,45]. In breast cancer, as reported by Sawant et al, MDSCs localized at bone metastatic sites, differentiated towards osteoclasts and contributed to bone destruction.…”