Arakawa Yukiyasu, Tamagawa-Mineoka Risa, Ueta Mayumi, Nakanishi Mari, Nishigaki Hiromi, Katoh Norito
Department of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Ophthalmology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Exp Dermatol. 2025 Mar;34(3):e70074. doi: 10.1111/exd.70074.
Ikaros, which is encoded by the Ikaros family zinc finger 1 (IKZF1) gene, is a zinc finger transcription factor. We have previously generated K5-Ikzf1-EGFP transgenic mice (Ikzf1 Tg) by introducing the IKZF1 isoform into epithelial cells expressing keratin 5, which develop patchy alopecia. However, there has been no detailed in vivo investigation of the function of IKZF1 in alopecia or of Ikaros expression in hair follicles of alopecia patients. Our aim was to investigate whether IKZF1 overexpression is involved in the pathogenesis of alopecia areata (AA) using Ikzf1 Tg and to examine Ikaros expression in human scalp skin. We grossly and histologically examined the alopecic lesions of Ikzf1 Tg and the skin of wild-type (WT) mice and the associated mRNA expression of inflammatory mediators. We also examined Ikaros' expression in human scalp skin. Grossly and histologically, we found that the Ikzf1 Tg developed AA-like lesions. Immunohistochemically, the hair follicles of the Ikzf1 Tg expressed high levels of the NKG2D ligand H60 and contained infiltrating CD8NKG2D T cells. Interleukin 15, tumour necrosis factor-α, CXC chemokine ligand (Cxcl)1, Cxcl10, Cxcl11, signal transducer and activator of transcription (STAT)1, STAT3, Janus kinase (JAK)1 and JAK3 mRNA expression were significantly higher in the alopecic lesions of the Ikzf1 Tg than in the WT mice. Ikzf1 Tg given corticosteroid injections exhibited hair regrowth. Immunohistochemical analysis of scalp hair follicles showed that Ikaros was more highly expressed in AA patients than in non-AA controls. Our study suggests that IKZF1 and Ikaros are involved in the pathogenesis of AA.
Ikaros由Ikaros家族锌指1（IKZF1）基因编码，是一种锌指转录因子。我们之前通过将IKZF1异构体导入表达角蛋白5的上皮细胞中，培育出了K5-Ikzf1-EGFP转基因小鼠（Ikzf1 Tg），这些小鼠会出现斑秃。然而，此前尚未对IKZF1在脱发中的功能或斑秃患者毛囊中Ikaros的表达进行详细的体内研究。我们的目的是利用Ikzf1 Tg研究IKZF1过表达是否参与斑秃（AA）的发病机制，并检测人头皮皮肤中Ikaros的表达。我们对Ikzf1 Tg的脱发损伤、野生型（WT）小鼠的皮肤进行了大体和组织学检查，并检测了炎症介质的相关mRNA表达。我们还检测了人头皮皮肤中Ikaros的表达。在大体和组织学上，我们发现Ikzf1 Tg出现了类似AA的损伤。免疫组织化学检测显示，Ikzf1 Tg的毛囊中高水平表达NKG2D配体H60，并含有浸润的CD8NKG2D T细胞。Ikzf1 Tg脱发损伤中白细胞介素15、肿瘤坏死因子-α、CXC趋化因子配体（Cxcl）1、Cxcl10、Cxcl11、信号转导和转录激活因子（STAT）1、STAT3、Janus激酶（JAK）1和JAK3的mRNA表达明显高于WT小鼠。给予皮质类固醇注射的Ikzf1 Tg出现了毛发生长。头皮毛囊的免疫组织化学分析显示，Ikaros在AA患者中的表达高于非AA对照。我们的研究表明，IKZF1和Ikaros参与了AA的发病机制。
