Abstract
IL-17-secreting helper CD4 T cells (Th17 cells) constitute a newly identified subset of helper CD4 T cells that play a key role in the development of rheumatoid arthritis (RA) in its animal models. Recently, several models of spontaneous RA, which elucidate the mechanism of RA onset, have been discovered. These animal models shed new light on the role of Th17 in the development of autoimmune arthritis. Th17 cells coordinate inflammation and promote joint destruction, acting on various cells, including neutrophils, macrophages, synovial fibroblasts, and osteoclasts. Regulatory T cells cannot control Th17 cells under conditions of inflammation. In this review, the pathogenic role of Th17 cells in arthritis development, which was revealed by the recent animal models of RA, is discussed.
Highlights
Type II Collagen-Induced ArthritisThe injection of cartilage constituents, such as type II collagen in complete Freund’s adjuvant, into genetically susceptible strains of mice induced synovitis and erosion that histologically resembled Rheumatoid arthritis (RA) (CIA, collagen-induced arthritis) [20]
After the discovery of CD4 T cells that produced IL-17 in the Rheumatoid arthritis (RA) synovium [16,17], studies using animal models revealed that Th17 cells are a lineage of CD4 T cells that are distinct from classical Th1 or Th2 cells, and play key roles in various autoimmune and inflammatory diseases [14,15]
Because tyrosine 759 is involved in the extracellular-signal-regulated kinase (ERK) signaling pathway mediated by gp130, and is essential for the suppressor of cytokine signaling (SOCS)-mediated negative feedback loop of signal transducer and activator of transcription 3 (STAT3) activation, STAT3 signaling is prolonged in gp130 F759 mice [64]. gp130 F759 mice suffer from autoimmune arthritis that clinically resembles RA [13]
Summary
The injection of cartilage constituents, such as type II collagen in complete Freund’s adjuvant, into genetically susceptible strains of mice induced synovitis and erosion that histologically resembled RA (CIA, collagen-induced arthritis) [20]. The sera of such mice contained abundant autoantibodies against type II collagen, and the disease could be induced in other mice by injecting anti-type II collagen antibodies (CAIA, anti-type II collagen antibody-induced arthritis) [21] (Figure 1). The final effectors of the disease in this animal model were autoantibodies (anti-type II collagen antibody), CD4 T cells were required for helping in the production of anti-type II collagen antibodies in B cells in the immunized mice (CIA). Th17 cells function as potent “osteoclastogenic” helper CD4 T cells that strongly stimulate the differentiation and activation of osteoclasts [42]
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