1. Department of General Intensive Care Unit, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310052, China.
2. Trauma Research Center, Fourth Medical Center of the Chinese PLA General Hospital, Beijing 100048, China.
3. State Key Laboratory of Kidney Disease, the Chinese PLA General Hospital, Beijing 100853, People's Republic of China.
*Yun Ge and Man Huang have contributed equally to this work.
Interleukin (IL)-34 is a cytokine discovered a few years ago and identified as the second colony-stimulating factor (CSF)-1 receptor (CSF-1R) ligand. Although CSF-1 and IL-34 share the same receptor through which they trigger similar effects, IL-34 also binds to receptors protein-tyrosine phosphatase (PTP)-ζ and syndecan-1. Thus, IL-34 is involved in several signaling pathways and participates in a wide array of biological actions. This review analyzes current studies on the role of IL-34 under physiological and pathological conditions, and explores its potential significance as a disease biomarker and therapeutic target. In physiological conditions, IL-34 expression is restricted to the microglia and Langerhans cells, with a fundamental role in cellular differentiation, adhesion and migration, proliferation, metabolism, and survival. It is released in response to inflammatory stimuli, such as pathogen-associated molecular patterns or pro-inflammatory cytokines, with effects over various immune cells, including monocytes, macrophages, and regulatory T cells that shape the immune microenvironment. Over the past decade, accumulating evidence has suggested a potent immune regulation of IL-34 in pathological states such as autoimmune diseases, cancer, transplant rejection, neurologic diseases, infections, and inflammatory diseases. Importantly, IL-34 may hold great promise for acting as a biomarker for monitoring disease severity and progression, and may serve as a new therapeutic target for the treatment of several diseases in clinical settings.
Keywords: interleukin-34, colony-stimulating factor-1 receptor ligand, immune response, inflammation, disease