Functions of interleukin-34 and its emerging association with rheumatoid arthritis

Immunology. 2016 Dec;149(4):362-373. doi: 10.1111/imm.12660. Epub 2016 Sep 23.

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic, synovial inflammation affecting multiple joints, finally leading to extra-articular lesions for which limited effective treatment options are currently available. Interleukin-34 (IL-34), recently discovered as the second colony-stimulating factor-1 receptor (CSF-1R) ligand, is a newly discovered cytokine. Accumulating evidence has disclosed crucial roles of IL-34 in the proliferation and differentiation of mononuclear phagocyte lineage cells, osteoclastogenesis and inflammation. Recently, IL-34 was detected at high levels in patients with active RA and in experimental models of inflammatory arthritis. Blockade of functional IL-34 with a specific monoclonal antibody can reduce the severity of inflammatory arthritis, suggesting that targeting IL-34 or its receptors may constitute a novel therapeutic strategy for autoimmune diseases such as RA. Here, we have comprehensively discussed the structure and biological functions of IL-34, and reviewed recent advances in our understanding of the emerging role of IL-34 in the development of RA as well as its potential utility as a therapeutic target.

Keywords: autoimmune; cytokine; inflammation; interleukin-34; rheumatoid arthritis.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / therapy
  • Humans
  • Immunotherapy / methods*
  • Immunotherapy / trends
  • Inflammation
  • Interleukins / immunology*
  • Interleukins / metabolism
  • Mice
  • Molecular Targeted Therapy
  • Mononuclear Phagocyte System
  • Osteogenesis
  • Receptors, Colony-Stimulating Factor / metabolism

Substances

  • Antibodies, Monoclonal
  • IL34 protein, human
  • Interleukins
  • Receptors, Colony-Stimulating Factor