BackgroundBlocking IL‐13 is highly efficacious in patients with Th2‐biased atopic dermatitis (AD), and recent clinical data have highlighted that targeting the T cell costimulatory molecules OX40 and OX40L (TNFSF4) holds promise for future treatment of AD.AimWe asked whether targeting another T cell costimulatory molecule, CD30L (TNFSF8), might also be a possible treatment option in AD.MethodsSingle‐cell RNA‐seq data from human AD skin lesions was analyzed to identify pathogenic IL‐13‐ or IL‐22‐producing T cells and assess expression of CD30 and its ligand in comparison to OX40 and its ligand. Additionally, a murine model of AD with repetitive exposure to house dust mite allergen was used to compare neutralizing antibodies against CD30L with those against IL‐13 or OX40L.ResultsAnalysis of several scRNA‐seq datasets from skin lesions of AD patients showed that transcripts for CD30 or CD30L were found expressed with OX40 or OX40L in the primary T cell populations that also expressed mRNA for IL13 and/or IL22. Suggesting that this could be therapeutically relevant, mice treated prophylactically with a blocking CD30L antibody were protected from developing maximal allergen‐induced AD features, including epidermal and dermal thickening, immune cell infiltration, and expression of AD‐related genes, similar to mice treated with a blocking IL‐13 antibody. Moreover, therapeutic neutralization of CD30L in mice with experimental AD also reduced all of the pathological skin lesion features to a comparable extent as blocking OX40L.ConclusionThese data suggest that targeting the CD30–CD30L axis might hold promise as a future therapeutic intervention in human AD, similar to targeting the OX40–OX40L axis.

中文翻译：

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CD30L 和 OX40L 的比较揭示了 CD30L 是特应性皮炎的有前途的治疗靶点


背景阻断 IL-13 对 Th2 偏倚的特应性皮炎 （AD） 患者非常有效，最近的临床数据强调，靶向 T 细胞共刺激分子 OX40 和 OX40L （TNFSF4） 有望在未来治疗 AD。AimWe 询问靶向另一种 T 细胞共刺激分子 CD30L （TNFSF8） 是否也可能是 AD 的一种可能的治疗选择。方法分析来自人类 AD 皮肤病变的单细胞 RNA-seq 数据，以识别致病性产生 IL-13 或 IL-22 的 T 细胞，并评估 CD30 及其配体与 OX40 及其配体相比的表达。此外，使用反复暴露于屋尘螨过敏原的 AD 小鼠模型来比较针对 CD30L 的中和抗体与针对 IL-13 或 OX40L 的中和抗体。结果对 AD 患者皮肤病变的几个 scRNA-seq 数据集的分析表明，在原代 T 细胞群中发现 CD30 或 CD30L 的转录物与 OX40 或 OX40L 一起表达，这些细胞群也表达 IL13 和/或 IL22 的 mRNA。表明这可能具有治疗相关性，用阻断 CD30L 抗体预防性治疗的小鼠被保护不会产生最大的过敏原诱导的 AD 特征，包括表皮和真皮增厚、免疫细胞浸润和 AD 相关基因的表达，类似于用阻断 IL-13 抗体治疗的小鼠。此外，在实验性 AD 小鼠中治疗性中和 CD30L 也减少了所有病理性皮肤病变特征，其程度与阻断 OX40L 相当。结论这些数据表明，靶向 CD30-CD30L 轴可能有望成为未来人类 AD 的治疗干预，类似于靶向 OX40-OX40L 轴。