Recent Insights Into the Role of Macrophages in Acute Gout

Abstract

Gout is a common type of inflammatory arthritis characterized by the presence of monosodium urate crystals (MSU) in the joints. Macrophages are believed to be involved in gout flares. It has long been recognized that resident macrophage and monocyte derived macrophages are distinct subsets and there have been attempts to investigate their roles in acute gout, respectively. Previous studies revealed that resident macrophages initiate and drive the inflammation, while monocyte derived macrophages differentiated into M1-like macrophages in response to MSU crystals. With the advancement of technologies, subpopulations of synovial resident macrophages have been defined with the characteristics more accurately described. Resident macrophages in the synovial lining layer showed an anti-inflammatory effect in rheumatoid arthritis, but specific Trpv4 depletion of them reduced MSU crystals induced murine arthritis. CD14+ monocytes in the synovial fluid from patients with gout exhibit phenotypes of anti-inflammatory as well as pro-inflammatory characteristics. Here, we review the main aspects of macrophages in the initiation and resolution of acute gout and try to clarify the specific role of each subpopulation. Building a reliable diagram of the effect of monocytes and macrophages during MSU crystals induced arthritis will bring us closer to targeting macrophages for improving the management of gout.

Bispecific antibodies tethering innate receptors induce human tolerant-dendritic cells and regulatory T cells

“…Next, DCIR and TLR2 expression in PBMC populations seemed to mainly result in the CD14 + pool ( Supplementary Figure 7C ). More than DCs, other monocyte populations infiltrate joints in both RA and gout ( 54 – 56 ). So, these populations, which are highly represented in inflammatory diseases, could be the main target of Bics because they are more numerous than DCs and their phenotype is sensitive to inflammation ( 57 ).…”

Phospholipase A2 regulates autophagy in gouty arthritis: proteomic and metabolomic studies

“…A gout is a group of clinical syndromes caused by guanine metabolism disorder or/and reduced uric acid excretion and continuous elevation of serum uric acid, which leads to the precipitation of urate crystals and deposition in tissues or organs [ 3 , 29 , 30 ]. The onset of the population is getting younger and younger, and the population of refractory gout is also increasing [ 4 ].The increase of blood uric acid in the human body caused by abnormal purine metabolism is closely related to genetic and environmental factors [ 30 , 31 ]. The biochemical basis of gout is the increase of blood uric acid in the body.…”

“…Clinically, AGA is most common in major joints, especially the first metatarsophalangeal, ankle, and foot joints. AGA will enter the intermittent symptomatic acute gouty arthritis (ISAGA) phase after uric acid lowering therapy (ULT) or resolve spontaneously [ 4 , 5 ]. It affects up to 1–2% of adults and is the most common form of inflammatory arthritis in men.…”

“…Fig 4. Metabolomic analysis of synovial fluid in the knee joint of patients with gout and normal group.…”

Protein phosphatase 2A regulates xanthine oxidase-derived ROS production in macrophages and influx of inflammatory monocytes in a murine gout model

“…The anti-inflammatory profile of fingolimod encompasses both NLRP3 inflammasome dependent and independent effects as shown by its ability to inhibit the secretion of pro-inflammatory cytokines that do not require NLRP3 inflammasome processing e.g., IL-6 and TNF-α in addition to IL-1β. Fingolimod may also regulate M1 macrophage polarization as it reduced the expression of a key M1 marker, iNOS ( Xue et al, 2018 ), while fingolimod’s effect on M-CSF secretion by macrophages is relevant to acute gout, given the cytokine’s role in priming resident macrophages in the setting of an acute flare ( Liu et al, 2022 ). Fingolimod also regulated the trafficking of immune cells in an in vivo model of acute gout.…”