Interactions of T helper cells with fibroblast‐like synoviocytes: Up‐regulation of matrix metalloproteinases by macrophage migration inhibitory factor from both Th1 and Th2 cells

Abstract

Conclusion. MIF is an important Th1 and Th2 cell-derived proinflammatory cytokine that stimulates MMP expression in FLS from arthritic mice, and therefore inhibition of MIF might be a promising target for novel therapeutic strategies in human RA.Macrophage migration inhibitory factor (MIF) is a structurally unique cytokine that is a critical mediator of several acute and chronic inflammatory diseases. Of note, MIF has been prominently detected in supernatants of T cells and in macrophages (1-5). Although it was originally described as a soluble factor that inhibits the undirected migration of macrophages, an effect known to participate in delayed-type hypersensitivity reactions (1,6), it has become evident that MIF functions in a chemokine-like manner to trigger the directed migration of leukocytes, an effect that involves CXCR2 ligation and the induction of monocyte chemoattractant protein 1 release by endothelial cells (7,8).

The IL-4 receptor α has a critical role in bone marrow–derived fibroblast activation and renal fibrosis

“…We have recently demonstrated that Th2 cytokines stimulate myeloid fibroblast activation via JAK3/STAT6 signaling pathway 13 . Although it is well-established that the biological effects of Th2 cytokines are regulated by IL-4Rα signaling 17, 18 , the precise role of IL-4Rα in activating myeloid fibroblasts and promoting renal fibrosis remains to be determined. In the present study, we have demonstrated that genetic disruption of IL-4Rα inhibits the bone marrow–derived fibroblast accumulation and myofibroblast formation in the kidney and reduces the development of renal fibrosis.…”

“…Th1 cells produce anti-fibrotic cytokines such as interferon γ (IFN-γ) that suppress myeloid fibroblasts differentiation, while Th2 cells produce the profibrotic cytokines such as IL-4 and IL-13 that promote myeloid fibroblasts differentiation 17–19 . IL-4 receptor α (IL-4Rα) is a key component of Th2 cytokine receptor, which mediates Th2 cytokines/signal transducer and activator of transcription 6 (STAT6) signaling pathway transduction and subsequent effector functions 20–22 .…”

Correlation between cold and hot pattern in traditional Chinese medicine and gene expression profiles in rheumatoid arthritis

“…The disease is characterized by synovial membrane hyperplasia and progressive destruction of arthritic joints, as well as inflammatory cell infiltration, including activated CD4 + T cells [2]. The CD4 + T cells play a crucial role in the pathogenesis of RA through their ability to stimulate the secretion of proinflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1, inducing immunoglobulin production and matrix metalloproteinase secretion leading to osteoclastogenesis [3].…”

Role of Cysteine Cathepsins in Joint Inflammation and Destruction in Human Rheumatoid Arthritis and Associated Animal Models

“…In contrast, Th2 cells, predominantly producing IL-4 and IL-10, are rarely found in arthritic joints. Anyway, both Th1 and Th2 cells can stimulate MMP expression in arthritic synovial fibroblasts by secretion of macrophage migration inhibitory factor [25]. Tumor necrosis factor alpha (TNFα) is considered as the main proinflammatory cytokine in the pathogenesis of RA [26].…”