Analysis of pathomechanisms of bullous pemphigoid and development of novel therapy by using humanized active mouse model

大疱性类天疱疮（BP）是最常见的自身免疫性水疱性疾病，优先发生在老年人。为了分析BP的确切病理机制并开发新的BP治疗策略，我们尝试开发一种新的BP活动性疾病模型，其中淋巴细胞、自身抗体和自身抗原已被人源化。首先，我们通过将COL 17人源化小鼠与免疫缺陷NOD-Scid小鼠杂交来产生COL 17人源化/Nod-Scid小鼠。接下来，我们使用BP患者的循环淋巴细胞开发了持续产生抗人COL 17 IgG 4抗体的CHO细胞，并将其注射到COL 17人源化/Nod-Scid小鼠中。注射CHO细胞可在受体小鼠体内长期存活，并在体内持续产生抗人COL 17 IgG 4。

Bullous pemphigoid (BP) is the most common autoimmune blistering disorder that preferentially occurs in elderly people. To analyze the precise pathomechanisms of BP and to develop a novel therapeutic strategy for BP, we tried to develop a novel active disease model for BP of which lymphocytes, autoantibodies and autoantigens have been humanized. First, we generated COL17-humanized/Nod-Scid mice by crossing COL17-humanized mice with immunodeficient NOD-Scid mice. Next, we developed CHO cells which persistently produce anti-human COL17 IgG4 antibodies using circulating lymphocytes from a BP patient, and injected them into COL17-humanized/Nod-Scid mice. Injected CHO cells could survive in the recipient mice for a long period and continuously produce anti-human COL17 IgG4 in vivo.