Laboratory of Medical Investigation LIM 56, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo 05403-000, Brazil.
Laboratory of Medical Investigation LIM 50, University of São Paulo Medical School, São Paulo 05403-000, Brazil.
Int J Mol Sci. 2023 Feb 28;24(5):4674. doi: 10.3390/ijms24054674.
Sézary syndrome (SS) is a rare and aggressive type of cutaneous T-cell lymphoma, with an abnormal inflammatory response in affected skin. The cytokines IL-1B and IL-18, as key signaling molecules in the immune system, are produced in an inactive form and cleave to the active form by inflammasomes. In this study, we assessed the skin, serum, peripheral mononuclear blood cell (PBMC) and lymph-node samples of SS patients and control groups (healthy donors (HDs) and idiopathic erythroderma (IE) nodes) to investigate the inflammatory markers IL-1B and IL-18 at the protein and transcript expression levels, as potential markers of inflammasome activation. Our findings showed increased IL-1B and decreased IL-18 protein expression in the epidermis of SS patients; however, in the dermis layer, we detected increased IL-18 protein expression. In the lymph nodes of SS patients at advanced stages of the disease (N2/N3), we also detected an enhancement of IL-18 and a downregulation of IL-1B at the protein level. Moreover, the transcriptomic analysis of the SS and IE nodes confirmed the decreased expression of and , whereas the pathway analysis indicated a further downregulation of -associated genes. Overall, the present findings showed compartmentalized expressions of IL-1B and IL-18 and provided the first evidence of their imbalance in patients with Sézary syndrome.
塞扎里综合征(SS)是一种罕见且侵袭性的皮肤 T 细胞淋巴瘤,受影响皮肤存在异常炎症反应。细胞因子 IL-1B 和 IL-18 作为免疫系统中的关键信号分子,以无活性形式产生,并通过炎性小体切割为活性形式。在这项研究中,我们评估了 SS 患者和对照组(健康供体(HD)和特发性红皮病(IE)节点)的皮肤、血清、外周单核血细 胞(PBMC)和淋巴结样本,以研究炎症标志物 IL-1B 和 IL-18 的蛋白和转录表达水平,作为炎性小体激活的潜在标志物。我们的研究结果显示,SS 患者表皮中 IL-1B 蛋白表达增加,IL-18 蛋白表达减少;然而,在真皮层,我们检测到 IL-18 蛋白表达增加。在 SS 患者疾病晚期(N2/N3)的淋巴结中,我们还在蛋白水平检测到 IL-18 的增强和 IL-1B 的下调。此外,SS 和 IE 节点的转录组分析证实了 和 的表达下调,而通路分析表明与相关基因的进一步下调。总体而言,这些发现显示了 IL-1B 和 IL-18 的分区表达,并首次提供了塞扎里综合征患者失衡的证据。