Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-0821, Japan.
Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-0821, Japan.
Biochem Biophys Res Commun. 2019 Aug 20;516(2):480-485. doi: 10.1016/j.bbrc.2019.06.094. Epub 2019 Jun 20.
Although Th17 cells are closely linked to cutaneous graft-versus-host-disease (GVHD) in mouse models, this association remains unclear in human GVHD. In this study, we established a novel xenogeneic cutaneous GVHD model using humanized mice. To induce the differentiation of human Th17 cells, we created transgenic NOG mice expressing human IL-1β and IL-23 cytokines (hIL-1β/23 Tg) and transplanted with human CD4 T cells. The pathologies of cutaneous GVHD, such as a decrease in body weight, alopecia, and T cell inflammation in the skin, were observed much earlier in hIL-1β/23 Tg mice compared with non-Tg mice after human CD4 T cell transplantation. In the skin of Tg mice, IL-17- and IFNγ-producing pathogenic Th17 cells were significantly accumulated. Furthermore, high infiltration of murine neutrophils was seen in the skin of Tg mice, but not non-Tg mice, which may have been the cause of the severe alopecia. CD4 T-cell-transferred hIL-1β/23 Tg mice were therefore highly sensitive models for inducing cutaneous GVHD mediated by human pathogenic Th17 cells.
尽管 Th17 细胞与小鼠模型中的皮肤移植物抗宿主病（GVHD）密切相关，但在人类 GVHD 中这种关联尚不清楚。在本研究中，我们使用人源化小鼠建立了一种新型的异种皮肤 GVHD 模型。为了诱导人 Th17 细胞的分化，我们创建了表达人白细胞介素-1β 和白细胞介素-23 细胞因子（hIL-1β/23 Tg）的 NOG 转基因小鼠，并移植了人 CD4 T 细胞。与非 Tg 小鼠相比，在人 CD4 T 细胞移植后，hIL-1β/23 Tg 小鼠更早地出现皮肤 GVHD 的病理变化，如体重下降、脱发和皮肤 T 细胞炎症。在 Tg 小鼠的皮肤中，IL-17 和 IFNγ 产生的致病性 Th17 细胞明显积聚。此外，在 Tg 小鼠的皮肤中可见大量浸润的鼠中性粒细胞，但在非 Tg 小鼠中则没有，这可能是严重脱发的原因。因此，CD4 T 细胞转导的 hIL-1β/23 Tg 小鼠是诱导由人致病性 Th17 细胞介导的皮肤 GVHD 的高度敏感模型。
