Blood natural killer cell deficiency reveals an immunotherapy strategy for atopic dermatitis
Blood natural killer cell deficiency reveals an immunotherapy strategy for atopic dermatitis
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DOI：
10.1126/scitranslmed.aay1005
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发表时间：
2020-02-26
影响因子：
17.1
通讯作者：
Kim, Brian S.
中科院分区：
文献类型：
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作者：
Mack, Madison R.;Brestoff, Jonathan R.;Kim, Brian S.
特应性皮炎（AD）是一种广泛分布的慢性皮肤病，与异常过敏性炎症有关。目前的治疗涉及广泛的或有针对性的免疫抑制策略。然而，增强免疫系统以控制疾病仍然未经测试。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，又可通过治疗改善。多维蛋白质和RNA分析揭示了与增强的NK细胞死亡相关的亚组水平变化。小鼠NK细胞缺乏与皮肤中增强的2型炎症相关，表明NK细胞在这种情况下发挥关键的免疫调节作用。在这些发现的基础上，我们使用了NK细胞增强白细胞介素-15（IL-15）超激动剂，并观察到小鼠AD样疾病的显着改善。这些发现揭示了IL-15超激动剂的一种以前未被认识的应用，目前正在开发用于癌症免疫治疗，作为AD的免疫策略。
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.