Synovial Macrophages: Past Life, Current Situation, and Application in Inflammatory Arthritis

Abstract

Inflammatory arthritis is an inflammatory disease that involves the joints and surrounding tissues. Synovial hyperplasia often presents when joints become inflamed due to immune cell infiltration. Synovial membrane is an important as well as a highly specific component of the joint, and its lesions can lead to degeneration of the joint surface, causing pain and joint disability or affecting the patients' quality of life in severe cases. Synovial macrophages (SMs) are one of the cellular components of the synovial membrane, which not only retain the function of macrophages to engulf foreign bodies in the joint cavity, but also interact with synovial fibroblasts (SFs), T cells, B cells, and other inflammatory cells to promote the production of a variety of pro-inflammatory cytokines and chemokines, such as TNF-α, IL-1β, IL-8, and IL-6, which are involved in the pathogenic process of inflammatory arthritis. SMs from different tissue sources have differently differentiated potentials and functional expressions. This article provides a summary on studies pertaining to SMs in inflammatory arthritis, and explores their role in its treatment, in order to highlight novel treatment modalities for the disease.

Keywords: arthritis; cell subsets; macrophages; synovial macrophages; synovial membrane; treatment.

Figure 1

Synovial structures in inflammatory arthritis. Synovial macrophages are mainly distributed in the lining layer of synovial tissue. During the onset of the disease, SMs can not only induce inflammation, but also perform immune monitoring.

Figure 2

The immunogenic role of synovial macrophages in inflammatory arthritis. Synovial macrophages interact with other immune cells through cytokines, chemokines, and inflammatory mediators to promote the activation, proliferation, and differentiation of lymphocytes, synovial fibroblasts, and osteoclasts in the synovium. TRM, tissue-resident memory T; SM, synovial macrophage; SF, synovial fibroblast; OC, osteoclast; AtoMs, arthritis-associated osteoclastogenic macrophages; IL-1RA, IL-1 receptor antagonists; IL-1βR, IL-1β receptor; IL-12R, IL-12 receptor; IL-23R, IL-23 receptor; IL-1R, IL-1 receptor; IL-6R, IL-6 receptor; IL-33R, IL-33 receptor; CD206L, CD206 ligand; CXCL, C-X-C motif chemokine ligand; CXCR, C-X-C motif chemokine receptor; CCL, C-C motif chemokine ligand; CCR, C-C motif chemokine receptor; TNF-α, tumor necrosis factor-α; IFN-γ, interferon-γ; OPG, osteoprotegerin; MerTK, tyrosine-protein kinase Mer; IRF5, interferon regulatory factor 5; BCA-1, B-cell-attracting chemokine; BCDF, B-cell differentiation factor; TLR, toll-like receptor; RANK, receptor activator of nuclear factor kappa-B; RANKL, receptor activator of nuclear factor kappa-B ligand; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; PG, prostaglandin.