The Proteomic and Clinical Flow Cytometry Unit, Bnai-Zion Medical Center, The Rappaport Faculty of Medicine, Technion, Haifa 31048, Israel.
Bnai-Zion Medical Center, The Division of Pathology, Haifa 31048, Israel.
Biomolecules. 2021 Mar 2;11(3):373. doi: 10.3390/biom11030373.
Patients with chronic spontaneous urticaria (CSU), an autoimmune disorder, show increased skin expression of IL-17A and can benefit from treatment with the anti-IL-17A biologic secukinumab. The mechanisms that drive IL-17A expression in CSU are currently unknown, but may involve Semaphorin5A (Sema5A). To explore the expression, role, and effects of Sema5A in CSU and its link to IL-17A. We investigated patients with CSU and healthy controls for skin expression of expressing peripheral T cells. Sema5A was highly expressed in the skin of CSU patients as compared to healthy control skin. Both CD4+ T cells and mast cells in CSU skin expressed Sema5A, and many of them expressed both Sema5A and IL-17A. Patients with CSU had significantly higher rates of IL-17A-expressing CD4+ T cells as compared to healthy controls. Incubation with Sema5A increased the rates of IL-17A-expressing CD4+ T cells in healthy controls to CSU levels. Sema5A may drive the expression and effects of IL-17A in CSU. Further studies in larger cohorts are needed to confirm the role of Sema5A in the pathogenesis of CSU and to explore its potential as a therapeutic target.
患有慢性自发性荨麻疹（CSU）的患者表现出 IL-17A 的皮肤表达增加，并可能受益于抗 IL-17A 生物制剂司库奇尤单抗的治疗。目前尚不清楚导致 CSU 中 IL-17A 表达的机制，但可能涉及 Sema5A（Semaphorin5A）。为了探索 Sema5A 在 CSU 中的表达、作用及其与 IL-17A 的关系。我们研究了 CSU 患者和健康对照者的外周 T 细胞的皮肤表达情况。与健康对照皮肤相比，CSU 患者的皮肤中 Sema5A 表达水平较高。CSU 皮肤中的 CD4+T 细胞和肥大细胞均表达 Sema5A，其中许多细胞同时表达 Sema5A 和 IL-17A。与健康对照组相比，CSU 患者的 IL-17A 表达 CD4+T 细胞的比率显著升高。与健康对照组相比，Sema5A 可增加 IL-17A 表达 CD4+T 细胞的比率。Sema5A 可能在 CSU 中驱动 IL-17A 的表达和作用。需要更大规模队列的进一步研究来证实 Sema5A 在 CSU 发病机制中的作用，并探索其作为治疗靶点的潜力。
