Interleukin-34, a comprehensive review

Abstract

IL-34 is a novel cytokine that was identified in 2008 in a comprehensive proteomic analysis as a tissue-specific ligand of CSF-1 receptor (CSF-1R). IL-34 exists in all vertebrates including fish, amphibians, birds, and mammals, showing high conservation among species. Structurally, IL-34 belongs to the short-chain helical hematopoietic cytokine family but shows no apparent consensus structural domains, motifs, or sequence homology with other cytokines. IL-34 is synthesized as a secreted homodimeric glycoprotein that binds to the extracellular domains of CSF-1R and receptor-type protein-tyrosine phosphatase-zeta (PTP-ζ) in addition to the chondroitin sulfate chains of syndecan-1. These interactions result in activating several signaling pathways that regulate major cellular functions, including proliferation, differentiation, survival, metabolism, and cytokine/chemokine expression in addition to cellular adhesion and migration. In the steady state, IL-34 contributes to the development and maintenance of specific myeloid cell subsets in a tissue-specific manner: Langerhans cells in the skin and microglia in the brain. In pathological conditions, changes in IL-34 expression-increased or decreased-are involved in disease pathogenesis and correlate with progression, severity, and chronicity. One decade after its discovery, IL-34 has been introduced as a newcomer to the big family of interleukins with specific physiological functions, critical pathological roles, and promising clinical applications in disease diagnosis and treatment. In this review, we celebrate the 10th anniversary of IL-34 discovery, introducing its biological characteristics, and discussing the importance of IL-34 signaling network in health and disease.

Interleukin‐34 mediated by hepatitis B virus X protein via CCAAT/enhancer‐binding protein α contributes to the proliferation and migration of hepatoma cells

“…As a newly identified cytokine, IL-34 is produced by a wide range of cells and participates in the survival, proliferation and differentiation of various cells. 12,13 Currently, the expression of IL-34 is identified as increase in patients with infection of various viruses, including HIV, 33 influenza A virus 34 and HCV. 35 15 Importantly, the increased IL-34 was associated with liver inflammation and fibrosis in HBV infection, and the results were consistent with the phenomenon observed in non-alcoholic fatty liver disease and chronic hepatitis C. 35,36 Besides these, IL-34 is shown to increase in different tumour cells, 26,[37][38][39] and related to the prognosis of various cancers.…”

“…Until now, collective evidence has demonstrated that IL-34 is involved in the development of viral infection, autoimmune diseases and cancers. 12,13 Importantly, recent studies show that IL-34 is involved in the HBV infection and associated with liver fibrosis. 14,15 Besides, the report from Zhou S et al shows that increased IL-34 is related to the poor survival and tumour recurrence in HCC patients, and modulates the invasion and metastasis of HCC cells via macrophages.…”

“…Three receptors, including CSF1-R, CD138 and PTP-ζ, were found to bind with IL-34. 12,13 We detected the mRNA and protein expression of these receptors in HBX and HBV-positive cells. The results indicated that HBX and HBV had no effect on CSF1-R.…”

Serum levels of interleukin‐34 and clinical correlation in patients with primary Sjögren's syndrome

“…To our knowledge, IL‐34 can promote the survival, proliferation and differentiation of mononuclear phagocytic lineage cells, including monocytes, macrophages, dendritic cells, Langerhans cells, osteoclasts, Kupffer cells, and microglia, providing crucial foundation for the role of IL‐34 in the process of immunoregulation in various disorders, including autoimmune diseases, inflammation, cancers and so on . Our previous studies have demonstrated that serum IL‐34 levels were significantly elevated in patients with RA as well as SLE, and the levels were associated with disease activity .…”

“…flammation, cancers and so on. 18 Our previous studies have demonstrated that serum IL-34 levels were significantly elevated in patients with RA as well as SLE, and the levels were associated with disease activity. 12,15 In addition, a recent study showed that serum IL-34 levels in patients with SSc were significantly higher than in healthy subjects.…”