Abstract
IL-25, a new member of the IL-17 cytokine family, is involved in type 2 immunity initiation and has been associated with the pathogenesis of rheumatoid arthritis (RA). However, its exact role remains unclear. Here, we aimed to analyse IL-25 expression in the serum and synovial fluid of RA patients and evaluated the correlations between serum IL-25 levels, clinical and laboratory values and inflammation cytokines. Additionally, we investigated whether IL-25 can suppress Th1/Th17 responses involved in RA pathogenesis. We further determined whether IL-25 can alleviate collagen-induced arthritis (CIA) development in mice and the underlying mechanisms using in vitro and in vivo experiments. Our results showed that IL-25 was upregulated in the serum and synovial fluid of RA patients. Increased serum IL-25 levels were associated with disease severity and inflammatory response in RA patients. Furthermore, IL-25 inhibited CD4+ T-cell activation and differentiation into Th17 cells, without affecting Th1 cells in human RA and CIA models. Administration of IL-25 could attenuate CIA development by Th17 suppression in an IL-13-dependent manner. Our findings indicate that IL-25 plays a potent immunosuppressive role in the pathogenesis of RA and CIA by downregulating Th17 cell response, and thus, may be a potential therapeutic agent for RA.
Highlights
Rheumatoid arthritis (RA) is a prevalent common autoimmune disease characterised by chronic inflammation of the joint and synovial hyperplasia and progressive destruction of articular cartilage and bone, which seriously influences a patient’s quality of life[1]
There is evidence that a broad range of cytokines is induced during the pathogenesis of rheumatoid arthritis (RA), including the proinflammatory cytokines, IFN-γ, TNF-αand IL-17A, as well as type 2 cytokines, IL-4 and IL-132
To determine whether IL-25 plays a regulatory role in RA, we first analysed the expression of this cytokine in RA patients
Summary
Rheumatoid arthritis (RA) is a prevalent common autoimmune disease characterised by chronic inflammation of the joint and synovial hyperplasia and progressive destruction of articular cartilage and bone, which seriously influences a patient’s quality of life[1]. The biological functions of IL-25 are markedly different from IL-17A and other IL-17 family cytokines It promotes Th2 cytokine responses and plays a critical role in the development of allergic diseases[3,9,10]. Wang et al.[15] showed in an experimental collagen II-induced arthritis (CIA) model that IL-25 was increased in serum and inflamed knee joints in CIA mice They reported a negative correlation between IL-17 and IL-25 at the peak of CIA, suggesting that IL-25 might contribute to the pathogenesis of RA through decreasing Th17 responses. To the best of our knowledge, this is the first study to provide evidence in both human RA and CIA mouse model that IL-25 is a critical anti-inflammatory cytokine in the pathogenesis of RA and may be considered as a potential therapeutic agent in the treatment of human RA
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