免疫相关疾病的确切发病机制仍不清楚。并且需要新的有效治疗选择来诱导这些疾病的缓解或治愈。利用免疫相关疾病患者来源的诱导多能干细胞(iPS)的基础研究有望成为阐明疾病发病机理和药物发现的有希望的平台。由于自身炎症性疾病通常是单基因的,基因突变影响细胞功能,患者来源的iPS细胞往往表现出疾病特异性表型.特别是,iPS细胞来源的单核细胞和巨噬细胞可用于功能实验,如炎性细胞因子的产生,并经常用于自身炎症性疾病患者的研究。另一方面,疾病特异性iPS细胞的利用对于自身免疫性疾病的研究不太成功。其中一个原因是自身免疫性疾病通常是多基因的,这使得确定哪些因素导致患者来源的iPS细胞的表型是由引起的具有挑战性的。另一个原因是分化一些与自身免疫相关的淋巴细胞的方案,如CD4+T细胞或B细胞,从iPS细胞尚未很好地建立。然而,几个小组报道了利用自身免疫性疾病患者来源的iPS细胞的研究,包括类风湿性关节炎患者,系统性红斑狼疮(SLE),和系统性硬化症。特别是,非造血细胞,如成纤维细胞和心肌细胞,分化自自身免疫患者来源的iPS细胞已显示出有希望的结果,为进一步研究发病机制。最近,我们的小组建立了一种分化产生干扰素α的树突状细胞的方法,可作为SLE病理模型应用。总之,患者来源的iPS细胞可以为免疫相关疾病领域的病理学研究和新药发现提供有前景的平台。
The precise pathogenesis of immune-related diseases remains unclear, and new effective therapeutic choices are required for the induction of remission or cure in these diseases. Basic research utilizing immune-related disease patient-derived induced pluripotent stem (iPS) cells is expected to be a promising platform for elucidating the pathogenesis of the diseases and for drug discovery. Since autoinflammatory diseases are usually monogenic, genetic mutations affect the cell function and patient-derived iPS cells tend to exhibit disease-specific phenotypes. In particular, iPS cell-derived monocytic cells and macrophages can be used for functional experiments, such as inflammatory cytokine production, and are often employed in research on patients with autoinflammatory diseases.On the other hand, the utilization of disease-specific iPS cells is less successful for research on autoimmune diseases. One reason for this is that autoimmune diseases are usually polygenic, which makes it challenging to determine which factors cause the phenotypes of patient-derived iPS cells are caused by. Another reason is that protocols for differentiating some lymphocytes associated with autoimmunity, such as CD4+T cells or B cells, from iPS cells have not been well established. Nevertheless, several groups have reported studies utilizing autoimmune disease patient-derived iPS cells, including patients with rheumatoid arthritis, systemic lupus erythematosus (SLE), and systemic sclerosis. Particularly, non-hematopoietic cells, such as fibroblasts and cardiomyocytes, differentiated from autoimmune patient-derived iPS cells have shown promising results for further research into the pathogenesis. Recently, our groups established a method for differentiating dendritic cells that produce interferon-alpha, which can be applied as an SLE pathological model. In summary, patient-derived iPS cells can provide a promising platform for pathological research and new drug discovery in the field of immune-related diseases.