Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Department of Dermatology and Allergy, University Hospital of Bonn, Germany.
Clin Immunol. 2020 Oct;219:108556. doi: 10.1016/j.clim.2020.108556. Epub 2020 Aug 8.
Atopic dermatitis (AD) is the most common inflammatory skin disease. It is characterized by a defective skin barrier and a Th2 dominated skin inflammation. The TNF family member a proliferation-inducing ligand (APRIL) and its receptors transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA) are expressed by immune cells and epithelial cells including keratinocytes. We demonstrate that APRIL expression is upregulated in the epidermis of skin lesions from patients with AD as well as in mouse skin undergoing allergic inflammation elicited by epicutaneous (EC) sensitization with the antigen ovalbumin. We show that APRIL from OVA sensitized mouse skin causes keratinocytes to upregulate the expression of IL-6, an inflammatory cytokine implicated in AD pathogenesis. These results suggest a role for APRIL in allergic skin inflammation and a potential role for APRIL blockade in treating AD.
特应性皮炎（AD）是最常见的炎症性皮肤病。它的特征是皮肤屏障缺陷和 Th2 主导的皮肤炎症。TNF 家族成员增殖诱导配体（APRIL）及其受体跨膜激活剂和钙调节剂和环亲环素配体相互作用物（TACI）和 B 细胞成熟抗原（BCMA）由免疫细胞和上皮细胞包括角质形成细胞表达。我们证明，AD 患者皮损表皮和经皮（EC）用抗原卵清蛋白致敏诱导的过敏炎症的小鼠皮肤中 APRIL 的表达上调。我们表明，来自 OVA 致敏小鼠皮肤的 APRIL 导致角质形成细胞上调炎症细胞因子 IL-6 的表达，该细胞因子与 AD 的发病机制有关。这些结果表明 APRIL 在过敏性皮肤炎症中的作用以及 APRIL 阻断在治疗 AD 中的潜在作用。
