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Blood natural killer cell deficiency reveals an immunotherapy strategy for atopic dermatitis.
Science Translational Medicine ( IF 17.1 ) Pub Date : 2020-02-26 , DOI: 10.1126/scitranslmed.aay1005
Madison R Mack 1, 2 , Jonathan R Brestoff 3 , Melissa M Berrien-Elliott 4 , Anna M Trier 1, 2 , Ting-Lin B Yang 1, 2 , Matthew McCullen 3 , Patrick L Collins 3 , Haixia Niu 1, 2 , Nancy D Bodet 1, 2 , Julia A Wagner 4 , Eugene Park 5 , Amy Z Xu 1, 2, 6 , Fang Wang 1, 2 , Rebecca Chibnall 2 , M Laurin Council 2 , Carrie Heffington 7 , Friederike Kreisel 3 , David J Margolis 8 , David Sheinbein 2 , Paola Lovato 9 , Eric Vivier 10, 11 , Marina Cella 3 , Marco Colonna 3 , Wayne M Yokoyama 5 , Eugene M Oltz 12 , Todd A Fehniger 4 , Brian S Kim 1, 2, 3
Affiliation  

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.

中文翻译:

血液中自然杀伤细胞的缺乏揭示了特应性皮炎的免疫治疗策略。

特应性皮炎(AD)是一种广泛的慢性皮肤疾病,伴有异常的过敏性炎症。当前的治疗涉及广泛的或靶向的免疫抑制策略。但是,增强免疫系统控制疾病的能力尚未得到检验。我们证明患有AD的患者存在血液自然杀伤(NK)细胞缺乏症,既具有诊断价值,又可以通过治疗改善。多维蛋白质和RNA分析揭示了与增强的NK细胞死亡相关的子集水平变化。鼠NK细胞的缺乏与皮肤中2型炎症的增强有关,这表明NK细胞在这种情况下起着至关重要的免疫调节作用。基于这些发现,我们使用了可增强NK细胞白介素15(IL-15)的超激动剂,并观察到小鼠AD样疾病的明显改善。
更新日期:2020-02-27
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