The role of interleukin‐6 signalling and its therapeutic blockage in skewing the T cell balance in rheumatoid arthritis

• Published in: Clinical and experimental immunology 2017-07, Vol.189 (1), p.12-20
• Main Authors: Schinnerling, K., Aguillón, J. C., Catalán, D., Soto, L.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibodies, Monoclonal, Humanized - therapeutic use; Arthritis, Rheumatoid - drug therapy; Autoimmune diseases; Cytokines; Helper cells; Humans; Immunoregulation; Interferon; Interferon-gamma - immunology; Interleukin 6; Interleukin 6 receptors; Interleukin-17 - immunology; Interleukin-6 - physiology; Lymphocytes; Lymphocytes T; Pharmaceutical industry; Plastic properties; Plasticity; Receptors, Interleukin-6 - antagonists & inhibitors; Review; Reviews; Rheumatoid arthritis; Signal Transduction; T cell plasticity; T-Lymphocytes, Regulatory - immunology; Th17 Cells - immunology; Th17/Treg balance; tocilizumab
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.12966

Summary Therapeutic blockage of cytokine signalling in autoimmune diseases has improved our understanding of the role of these cytokines in triggering, shaping and perpetuating autoimmune responses. In rheumatoid arthritis (RA), immunopathology is driven by a predominance of arthritogenic T helper cells secreting interferon‐γ [T helper type 1 (Th1)] and interleukin (IL)‐17 (Th17) over regulatory T cells (Treg). The pleiotropic cytokine IL‐6 is crucial to the differentiation of Th17 cells and the balance between pathogenic Th17 and protective Treg. Targeting the IL‐6 receptor (IL‐6R) by humanized antibodies improves signs and symptoms of RA, and has provided new insights into the mechanisms of inflammation and immune regulation. Here we review current evidence on the role of IL‐6 in the pathogenesis of RA and the molecular consequences of IL‐6R blockage in disease, with special focus on the Th17/Treg balance and plasticity. In rheumatoid arthritis patients, IL‐6 exerts systemic effects on multiple tissues and cells of the immune system. Among other functions, IL‐6 promotes the expansion of IFN‐gamma and IL‐17 producing effector T cells, and prevents the generation of regulatory T cells. The blockade of lL‐6 or its receptor with therapeutic antibodies can restore the equilibrium between these populations, and thus contribute to arrest the inflammatory and degenerative consequences of the disease.