Mack Madison R, Brestoff Jonathan R, Berrien-Elliott Melissa M, Trier Anna M, Yang Ting-Lin B, McCullen Matthew, Collins Patrick L, Niu Haixia, Bodet Nancy D, Wagner Julia A, Park Eugene, Xu Amy Z, Wang Fang, Chibnall Rebecca, Council M Laurin, Heffington Carrie, Kreisel Friederike, Margolis David J, Sheinbein David, Lovato Paola, Vivier Eric, Cella Marina, Colonna Marco, Yokoyama Wayne M, Oltz Eugene M, Fehniger Todd A, Kim Brian S
Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Sci Transl Med. 2020 Feb 26;12(532). doi: 10.1126/scitranslmed.aay1005.
Atopic dermatitis (AD) is a widespread, chronic skin disease associated with aberrant allergic inflammation. Current treatments involve either broad or targeted immunosuppression strategies. However, enhancing the immune system to control disease remains untested. We demonstrate that patients with AD harbor a blood natural killer (NK) cell deficiency that both has diagnostic value and improves with therapy. Multidimensional protein and RNA profiling revealed subset-level changes associated with enhanced NK cell death. Murine NK cell deficiency was associated with enhanced type 2 inflammation in the skin, suggesting that NK cells play a critical immunoregulatory role in this context. On the basis of these findings, we used an NK cell-boosting interleukin-15 (IL-15) superagonist and observed marked improvement in AD-like disease in mice. These findings reveal a previously unrecognized application of IL-15 superagonism, currently in development for cancer immunotherapy, as an immunotherapeutic strategy for AD.
特应性皮炎（AD）是一种广泛存在的慢性皮肤病，与异常的过敏性炎症相关。目前的治疗方法包括广泛或靶向免疫抑制策略。然而，增强免疫系统来控制疾病仍未得到验证。我们证明，AD患者存在血液自然杀伤（NK）细胞缺陷，这既具有诊断价值，又会随着治疗而改善。多维蛋白质和RNA分析揭示了与NK细胞死亡增加相关的亚群水平变化。小鼠NK细胞缺陷与皮肤中2型炎症增强有关，表明NK细胞在此背景下发挥关键的免疫调节作用。基于这些发现，我们使用了一种增强NK细胞的白细胞介素-15（IL-15）超级激动剂，并观察到小鼠类AD疾病有显著改善。这些发现揭示了目前正在开发用于癌症免疫治疗的IL-15超级激动剂作为AD免疫治疗策略的一种以前未被认识的应用。
