Schettini Natale, Pacetti Lucrezia, Corazza Monica, Borghi Alessandro
From the Section of Dermatology and Infectious Diseases, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
Dermatitis. 2025 Jan-Feb;36(1):28-36. doi: 10.1089/derm.2024.0058. Epub 2024 May 3.
OX40 is a co-stimulatory immune checkpoint molecule that promotes the activation and the effector function of T lymphocytes through interaction with its ligand (OX40L) on antigen-presenting cells. OX40-OX40L axis plays a crucial role in Th1 and Th2 cell expansion, particularly during the late phases or long-lasting response. Atopic dermatitis is characterized by an immune dysregulation of Th2 activity and by an overproduction of proinflammatory cytokines such as interleukin (IL)-4 and IL-13. Other molecules involved in its pathogenesis include thymic stromal lymphopoietin, IL-33, and IL-25, which contribute to the promotion of OX40L expression on dendritic cells. Lesional skin in atopic dermatitis exhibits a higher level of OX40L+-presenting cells compared with other dermatologic diseases or normal skin. Recent clinical trials using antagonizing anti-OX40 or anti-OX40L antibodies have shown symptom improvement and cutaneous manifestation alleviation in patients with atopic dermatitis. These findings suggest the relevance of the OX40-OX40L axis in atopic dermatitis pathogenesis.
OX40是一种共刺激免疫检查点分子，它通过与抗原呈递细胞上的配体（OX40L）相互作用来促进T淋巴细胞的活化及其效应功能。OX40-OX40L轴在Th1和Th2细胞扩增中起关键作用，尤其是在晚期或持久反应期间。特应性皮炎的特征是Th2活性的免疫失调以及促炎细胞因子如白细胞介素（IL）-4和IL-13的过度产生。其发病机制中涉及的其他分子包括胸腺基质淋巴细胞生成素、IL-33和IL-25，它们有助于促进树突状细胞上OX40L的表达。与其他皮肤病或正常皮肤相比，特应性皮炎的皮损皮肤中OX40L+呈递细胞水平更高。最近使用抗OX40或抗OX40L抗体进行的临床试验表明，特应性皮炎患者的症状有所改善，皮肤表现得到缓解。这些发现表明OX40-OX40L轴与特应性皮炎发病机制相关。
