Ustekinumab treats psoriasis by suppressing RORC and T-box but its suppression of GATA restrains its efficacy

Psoriasis is a T-cell mediated disease that involves IL-23/Th17 and IL-12/Th1 axes. Ustekinumab, a fully human monoclonal antibody targeting the p40 subunit of both IL-12 and IL-23, has proven to be efficient and safe for treating patients with psoriasis. Yet, there have been no reports with human skin/blood samples that would elucidate the molecular mechanisms by which ustekinumab calms psoriasis skin lesions. To investigate the efficacy and molecular pathway (RORC, t-BOX and GATA) of ustekinumab in treating patients with psoriasis skin lesions. A total of 30 patients with psoriasis were randomized into placebo group and treatment group. PASI of each patient was calculated at 0, 12 and 24 weeks post-treatment. The mRNA levels of RORC, t-BOX and GATA in peripheral blood mononuclear cells separated from patients’ whole blood were analyzed using qPCR. Decreased mRNA of RORC, t-BOX and GATA were observed after continuous injections, indicating that ustekinumab exerts its effect by interacting with these molecules; while no significant difference in foxp3 mRNA levels were found between placebo group and treatment group.

银屑病（Psoriasis）是一种T细胞介导的疾病，涉及白细胞介素23（IL-23）/辅助性T细胞17（Th17）与白细胞介素12（IL-12）/辅助性T细胞1（Th1）信号轴。乌司奴单抗（Ustekinumab）是一种靶向IL-12和IL-23共有的p40亚基的全人源单克隆抗体，已被证实用于银屑病患者治疗时安全有效。然而，目前尚无针对人体皮肤/血液样本的研究阐明乌司奴单抗缓解银屑病皮损的分子机制。为探究乌司奴单抗治疗银屑病皮损的疗效及其分子通路（RORC、t-BOX与GATA），本研究将30例银屑病患者随机分为安慰剂组与治疗组，分别于治疗后0、12及24周计算每位患者的PASI（银屑病面积与严重性指数，Psoriasis Area and Severity Index）评分，采用qPCR（实时定量聚合酶链反应，quantitative PCR）分析从患者全血中分离的外周血单个核细胞内RORC、t-BOX及GATA的mRNA水平。持续注射给药后，观测到RORC、t-BOX与GATA的mRNA表达水平均下调，表明乌司奴单抗通过与这些分子相互作用发挥治疗效应；而安慰剂组与治疗组的foxp3 mRNA水平无显著差异。