Interleukin 27 Signaling in Rheumatoid Arthritis Patients: Good or Evil?

Abstract

The occurrence and development of rheumatoid arthritis (RA) is regulated by numerous cytokines. Interleukin 27 (IL-27) is a soluble cytokine that exerts biological effects by regulating the Janus tyrosine kinase (JAK)/signal transducer and activator of the transcription (STAT) signaling pathway via the IL-27 receptor. IL-27 is known for its pleiotropic roles in modulating inflammatory responses. Previous studies found that IL-27 levels are elevated in RA blood, synovial fluid, and rheumatoid nodules. Cellular and animal experiments indicated that IL-27 exerts multiple regulatory functions in RA patients via different mechanisms. IL-27 inhibits ectopic-like structure (ELS) formation and CD4+ T helper type 2 (Th2) cell, CD4+ T helper type 17 (Th17) cell, and osteoclast differentiation in RA, contributing to alleviating RA. However, IL-27 promotes Th1 cell differentiation, which may exacerbate RA synovitis. Moreover, IL-27 also acts on RA synovial fibroblasts (RA-FLSs) and regulatory T cells (Tregs), but some of its functions are unclear. There is currently insufficient evidence to determine whether IL-27 promotes or relieves RA. Targeting IL-27 signaling in RA treatment should be deliberate based on current knowledge.

TNFR1-mediated senescence and lack of TNFR2-signaling limit human intervertebral disc cell repair in back pain conditions

“…4C). GSEA identified these DEGs to be biological processes enriched for IL-27 mediated signaling pathway, which has multiple effects in modulating inflammatory responses ( 45 ). Additional enriched biological processes were related to Regulation of Neuroinflammatory Response, and Response to Cytokine, demonstrating a shift in the inflammatory pathways activated by CM (Fig.…”

Multiple-Factors-Induced Rheumatoid Arthritis Synoviocyte Activation Is Attenuated by the α2-Adrenergic Receptor Agonist Dexmedetomidine

“…Owing to the inhibitory effect of Dex on RA-FLS migration, we determined the inhibitory effect of Dex on RA-associated factors to verify its therapeutic endpoint. Various RA-associated inflammatory factors, such as IL-6 , IL-8 , IL-1β , IL-27 , and COX-2 [ 18 , 32 ], RA-associated joint remodeling factor Dickkopf-1 ( DKK-1 ) [ 33 ], and osteoclastogenesis factor receptor activator of nuclear factors κB ligand ( RANKL ) [ 34 ] in multiple-input-stimulated RA-FLSs with or without Dex were evaluated in a transwell culture system. The multiple inputs were found to stimulate RA-associated inflammatory and joint factors, whereas Dex attenuated the enhanced mRNA expression of these factors ( Figure 6 a–c).…”

A compendium of mitochondrial molecular characteristics provides novel perspectives on the treatment of rheumatoid arthritis patients

“…Recent research indicates that IL-27 may play a role in the pathogenesis of RA through various direct and indirect regulatory pathways. Specifically, IL-27 signaling may impact the development of RA by modulating CD4 + T cell differentiation, suppressing monocytes/macrophages and osteoclasts within the joint cavity, disrupting interactions between synovial ectopic lymphoid structures (ELS) and Th17 cells, and regulating inflammation mediated by RA synovial fibroblasts (RA-FLS) [ 38 , 39 ]. These findings indicate that the hedgehog signaling pathway and interleukin_27 signaling are significantly enriched in the innate lymphocyte-rich subtype, emphasizing the superior outcomes of anti-TNF and Infliximab.…”