Research ArticleATOPY

Blood natural killer cell deficiency reveals an immunotherapy strategy for atopic dermatitis

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Science Translational Medicine  26 Feb 2020:
Vol. 12, Issue 532, eaay1005
DOI: 10.1126/scitranslmed.aay1005

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Nurturing NK cells to treat atopic dermatitis

The skin condition atopic dermatitis (AD) is driven by a type 2 immune response. Mack et al. performed high-dimensional immune profiling of patients with AD and revealed deficiencies in certain subsets of natural killer (NK) cells. NK cells showed signs of activation-induced cell death and were restored in patients that responded to immunotherapy. Circulating NK cells were also decreased in a mouse AD model; boosting NK cells with an IL-15 superagonist ameliorated symptoms in the mice. These results suggest that strategies to restore NK cells could help rebalance immunity in AD.

Abstract

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.

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