Therapy targeting folate receptor beta expressing macrophages in chronic inflammation

我们分别在甲基化BSA诱导的关节炎和博莱霉素诱导的皮肤纤维化模型中，使用针对FR β的重组免疫毒素，评估了消耗表达FR β的巨噬细胞的抗关节原性和抗纤维化作用。 在第29天通过皮肤厚度和羟脯氨酸含量的变化来评估皮肤纤维化。在第9天通过定量实时RT-PCR评估处理皮肤中的TGF β 1 mRNA水平。抗FR β-PE 38处理导致表达FR β的巨噬细胞数量的急剧减少。此外，皮肤厚度和羟脯氨酸含量显着降低。TGF β 1 mRNA水平在治疗后也下调。与FR β阴性巨噬细胞相比，TGF β 1表达在FR β表达巨噬细胞中富集。 抗FR β-PE 38治疗有效地耗尽了表达FR β的巨噬细胞，因此减轻了BLM诱导的皮肤纤维化。

We assessed the antiarthrogenic and the antifibrotic effects ofdepletion of FRbeta-expressing macrophages in methylated BSA induced arthritis and bleomycin induced skin fibrosis models using a recombinant immunotoxin to FRbeta, respectively. Skin fibrosis was evaluated by the change of skin thickness and hydroxyproline content on Day 29. The TGFbeta1 mRNA levels in the treated skin were assessed by quantitative real-time RT-PCR on Day 9. Anti-FRbeta-PE38 treatment led to a dramatic reduction in the number of FRbeta-expressing macrophages. Additionally, skin thickness and hydroxyproline content, were markedly reduced. TGFbeta1 mRNA levels were also down-regulated after the treatment. TGFbeta1 expression was enriched in FRbeta-expressing macrophages compared with FRbeta-negative macrophages. Anti-FRbeta-PE38 treatment efficiently depleted FRbeta-expressing macrophages and consequently alleviated BLM-induced skin fibrosis.