In a new study entitled “Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis” researchers discovered that the cytokine interleukin-27 (IL-27) inhibits the formation of ectopic lymphoid-like structures (ELSs) in patients with rheumatoid arthritis, thereby preventing ELSs to contribute to disease progression through recruitment and maturation of inflammatory cells to inflamed tissues. The study was published in the Journal of Experimental Medicine.
Rheumatoid arthritis (RA) is a chronic inflammatory disorder that mainly affects small joints in the hands and feet due to chronic inflammation of the synovium, a thin layer of tissue which lines the joint space. In a subset of RA patients (approximately 40%), inflamed joints develop ectopic lymphoid-like structures (ELSs) that contribute to the disease pathology. Specifically, these aggregates are associated with disease severity, activation of key immune cells (T and B cells) and autoantibody production.
In this study, researchers investigated the role of IL-27 in RA synovial pathology, since previous studies reported that IL-27 halted the expansion of a subset of inflammatory T cells (CD4+ T helper 17). The team used mice deficient for the Il27ra gene (encoding IL-27 receptor α chain), used as a model for antigen-induced arthritis, observing that these mice exhibited more severe RA when compared to wild-type (that express the functional Il27ra gene) controls. In Il27ra deficient mice researchers observed increased expression of pro-inflammatory cytokines in mice synovium, hypertrophy, and both cartilage and bone degradation. In agreement with IL-27 controlling T helper 17 responses, the team observed that knock-out mice for IL-27 had higher levels of the cytokine expressed in inflamed synovium.
These findings were further validated in RA patients’ synovial tissues, where they found that low levels of IL-27 increased the incidence of ELSs. Additionally, IL-27 levels and infiltration of inflammatory T cells (CD3+ and CD20+ cells) and synovitis (i.e., inflammation of the synovial membrane) were inversely correlated: low IL-27 levels promoted inflammation.
These data suggest IL-27 may negatively regulate the occurrence of ELSs in RA patients, and the authors propose that measuring IL-27 levels in this population of patients can potentially be used as a biomarker for diffuse synovial histopathology and a potential target for future therapeutic interventions in RA.