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Published on: February 21, 2018
IL-34 and CSF-1: similarities and differences
Yuko Nakamichi1, Nobuyuki Udagawa, Naoyuki Takahashi
1Institute for Oral Science, Matsumoto Dental University, 1780 Hiro-oka Gobara, Shiojiri, Nagano, 399-0781, Japan, nakamichi@po.mdu.ac.jp.
Insights
Colony-stimulating factor-1 (CSF-1) and Interleukin-34 (IL-34) are ligands for the CSF-1 receptor, impacting mononuclear phagocyte development. This review compares their distinct in vivo functions and expression patterns.
Area of Science:
- Immunology
- Cell Biology
- Developmental Biology
Background:
- Colony-stimulating factor-1 (CSF-1) regulates mononuclear phagocyte development, including macrophages, dendritic cells (DCs), and osteoclasts.
- Interleukin-34 (IL-34) is a recently identified alternative ligand for the CSF-1 receptor (CSF-1R).
- Genetic deficiencies in CSF-1R and CSF-1 reveal distinct impacts on immune cell populations.
Purpose of the Study:
- To compare the functional similarities and differences between IL-34 and CSF-1 in vivo.
- To elucidate the distinct biological roles of IL-34 and CSF-1.
- To analyze their spatiotemporal expression patterns.
Main Methods:
- Review of existing literature and functional proteomics data.
- Comparative analysis of phenotypes in genetically modified mouse models (CSF-1R⁻/⁻, CSF-1(op/op), IL-34⁻/⁻).
- Examination of in vivo biological functions and expression patterns.
Main Results:
- CSF-1R deficiency has more severe consequences than CSF-1 deficiency.
- IL-34 deficiency primarily affects Langerhans cells (LCs) and microglia.
- CSF-1 and IL-34 exhibit distinct spatiotemporal expression and biological functions.
Conclusions:
- IL-34 and CSF-1, while both binding CSF-1R, have unique and non-redundant roles in vivo.
- Understanding their distinct functions is crucial for comprehending mononuclear phagocyte biology.
- Further research into IL-34 and CSF-1 pathways can inform therapeutic strategies.
Abstract:
Colony-stimulating factor-1 (CSF-1) is widely expressed and considered to regulate the development, maintenance, and function of mononuclear phagocyte lineage cells such as monocytes, macrophages, dendritic cells (DCs), Langerhans cells (LCs), microglia, and osteoclasts. Interleukin-34 (IL-34) was recently identified as an alternative ligand for the CSF-1 receptor (CSF-1R) through functional proteomics experiments. It is well established that the phenotype of CSF-1R-deficient (CSF-1R⁻/⁻) mice is more severe than that of mice bearing a spontaneous null mutation in CSF-1 (CSF-1(op/op)). CSF-1R⁻/⁻ mice are severely depleted of macrophages and completely lack LCs, microglia, and osteoclasts during their lifetime. In contrast, CSF-1(op/op) mice exhibit late-onset macrophage development and osteoclastogenesis, whereas they show modestly reduced numbers of microglia and a relatively normal LC development. In contrast, IL-34-deficient (IL-34⁻/⁻) mice show a marked reduction of LCs and a decrease in microglia. IL-34 and CSF-1 display different spatiotemporal expression patterns and have distinct biological functions. In this review, we focus on the functional similarities and differences between IL-34 and CSF-1 in vivo.
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