Kyoto R&D Center, Maruho Co., Ltd., Kyoto, Japan.
Kyoto R&D Center, Maruho Co., Ltd., Kyoto, Japan.
J Dermatol Sci. 2021 Oct;104(1):21-29. doi: 10.1016/j.jdermsci.2021.09.001. Epub 2021 Sep 3.
C3H/HeJ mouse models progress gradually in hair loss from acute to chronic phase and reflect the symptoms of patients with alopecia areata (AA). However, the underlying pathological characteristics alteration associated with disease progression and autoantigens remain unclear.
We aimed at elucidating the pathological differences between acute and chronic-AA in the C3H/HeJ mouse model.
We analyzed populations of PBMCs, skin-draining lymph node (SDLN) cells, and cutaneous cells of AA mice using flow cytometry. The cytokine and chemokine expressions in the serum and skin were determined using multiplex assay and qPCR. The antibody serum levels were determined using ELISA and the antigen-specific T cells were detected using the MHC class I tetramer.
The CD8NKG2D T and CD8 T cell percentage in the chronic-AA SDLNs or among the unaffected and acute-AA mice PBMCs increased. The Th1 and CD4 T cell percentage in the SDLNs and among PBMCs increased in the unaffected and AA mice. The percentage of CD8 T/T cells and MHC class I expression increased in the lesions of acute-AA or the non-lesions and lesions of chronic-AA. The Th1 cells, dendritic cell-related cytokines, CD11c cells and MHC class II expression increased in the skin of AA mice. The antibody levels and TYRP2 and tyrosinase-specific CD8 T cell percentages were upregulated in AA mice.
These results suggest that the CD8 and CD4 T cell subpopulations, cytokine and chemokine expressions differ between the disease phases. Moreover, TYRP2 and tyrosinase are potential autoreactive targets in the AA mouse model.
C3H/HeJ 小鼠模型从急性脱发期逐渐进展为慢性脱发期，反映了斑秃（AA）患者的症状。然而，与疾病进展和自身抗原相关的潜在病理特征改变尚不清楚。
我们旨在阐明 C3H/HeJ 小鼠模型中急性和慢性 AA 之间的病理差异。
我们使用流式细胞术分析 AA 小鼠的 PBMCs、皮肤引流淋巴结（SDLN）细胞和皮肤细胞群体。使用多重分析和 qPCR 测定血清和皮肤中的细胞因子和趋化因子表达。使用 ELISA 测定抗体血清水平，使用 MHC 类 I 四聚体检测抗原特异性 T 细胞。
慢性 AA SDLN 或未受影响和急性 AA 小鼠 PBMC 中的 CD8NKG2D T 和 CD8 T 细胞百分比增加。SDLN 和未受影响及 AA 小鼠 PBMC 中的 Th1 和 CD4 T 细胞百分比增加。急性 AA 或慢性 AA 的非病变和病变中的 CD8 T/T 细胞百分比和 MHC 类 I 表达增加。AA 小鼠皮肤中的 Th1 细胞、树突状细胞相关细胞因子、CD11c 细胞和 MHC 类 II 表达增加。AA 小鼠中的抗体水平和 TYRP2 和酪氨酸酶特异性 CD8 T 细胞百分比增加。
这些结果表明，CD8 和 CD4 T 细胞亚群、细胞因子和趋化因子表达在疾病阶段之间存在差异。此外，TYRP2 和酪氨酸酶是 AA 小鼠模型中的潜在自身反应性靶标。
