Kyoto R&D Center, Maruho Co., Ltd., Kyoto, Japan.
Kyoto R&D Center, Maruho Co., Ltd., Kyoto, Japan.
J Dermatol Sci. 2021 Jun;102(3):177-183. doi: 10.1016/j.jdermsci.2021.04.009. Epub 2021 May 4.
Alopecia areata (AA) is an autoimmune disease resulting in non-scarring hair loss. Animal models are useful means to identify candidates for therapeutic agents. The C3H/HeJ mouse AA model induced via transferring cultured lymphoid cells isolated from AA-affected mice is widely used for AA research. However, this conventional method requires the continuous breeding of AA mice.
We aimed to establish a new method to generate AA model using the transfer of cryopreserved cells, which allows the rapid induction of a large number of AA mice when needed.
We cryopreserved lymph node cells soon after isolation from AA-affected mice and injected thawed-cultured cells into recipient mice. H&E staining, immunohistochemical staining, quantitative real-time PCR and ELISA were conducted to identify pathological characteristics. Flow cytometry was performed to reveal the profile of transferred cells.
More than 90 % of recipient mice developed AA-like hair loss and showed inflammatory cell infiltration around anagen hair follicles, markedly increased mRNA expressions of interferon-γ, CXCL11, and granzyme B, and elevated interferon-α protein levels in the skin compared with naïve mice. Higher percentages of effector memory T cells and dendritic cells in transferred cells resulted in a higher incidence of AA.
This is the first report to establish a method for generating AA mice using cryopreserved lymphocytes. These AA mice have similar pathological characteristics to AA mice generated with the conventional method and AA patients. This convenient and reproducible method is expected to be valuable for AA study.
斑秃(AA)是一种自身免疫性疾病,导致非瘢痕性脱发。动物模型是鉴定治疗药物候选物的有用手段。通过转移来自 AA 受累小鼠的培养淋巴细胞建立的 C3H/HeJ 小鼠 AA 模型广泛用于 AA 研究。然而,这种常规方法需要 AA 小鼠的连续繁殖。
我们旨在建立一种使用冷冻保存细胞转移来生成 AA 模型的新方法,该方法允许在需要时快速诱导大量 AA 小鼠。
我们在从 AA 受累小鼠分离后不久就对淋巴结细胞进行冷冻保存,并将解冻培养的细胞注入受体小鼠中。进行 H&E 染色、免疫组织化学染色、定量实时 PCR 和 ELISA 以鉴定病理特征。进行流式细胞术以揭示转移细胞的特征。
超过 90%的受体小鼠出现 AA 样脱发,并显示出在生长期毛囊周围有炎症细胞浸润,与正常小鼠相比,皮肤中干扰素-γ、CXCL11 和颗粒酶 B 的 mRNA 表达明显增加,干扰素-α 蛋白水平升高。转移细胞中效应记忆 T 细胞和树突状细胞的比例较高导致 AA 的发生率较高。
这是首次报道使用冷冻保存的淋巴细胞建立 AA 小鼠的方法。这些 AA 小鼠具有与常规方法产生的 AA 小鼠和 AA 患者相似的病理特征。这种方便且可重复的方法有望对 AA 研究具有重要价值。