受体
生物
细胞因子
病态的
下调和上调
信号转导
蛋白质酪氨酸磷酸酶
免疫疗法
癌症研究
细胞生物学
免疫学
神经科学
医学
内科学
免疫系统
基因
遗传学
作者
Ryo Otsuka,Haruka Wada,K. Seino
标识
DOI:10.1016/j.smim.2021.101517
摘要
IL-34 is a cytokine that shares one of its receptors with CSF-1. It has long been thought that CSF-1 receptor (CSF-1R) receives signals only from CSF-1, but the identification of IL-34 reversed this stereotype. Regardless of low structural homology, IL-34 and CSF-1 emanate similar downstream signaling through binding to CSF-1R and provoke similar but different physiological events afterward. In addition to CSF-1R, protein-tyrosine phosphatase (PTP)-ζ and Syndecan-1 were also identified as IL-34 receptors and shown to be at play. Although IL-34 expression is limited to particular tissues in physiological conditions, previous studies have revealed that it is upregulated in several diseases. In cancer, IL-34 is produced by several types of tumor cells and contributes to therapy resistance and disease progression. A recent study has demonstrated that tumor cell-derived IL-34 abrogates immunotherapy efficacy through myeloid cell remodeling. On the other hand, IL-34 expression is downregulated in some brain and dermal disorders. Despite accumulating insights, our understanding of IL-34 may not be even close to its nature. This review aims to comprehensively describe the physiological and pathological roles of IL-34 based on its similarity and differences to CSF-1 and discuss the rationale for its disease-dependent expression pattern.
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