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

Madison R. Mack, Jonathan R. Brestoff, Melissa M. Berrien-Elliott, Anna M. Trier, Ting Lin B. Yang, Matthew McCullen, Patrick L. Collins, Haixia Niu, Nancy D. Bodet, Julia A. Wagner, Eugene Park, Amy Z. Xu, Fang Wang, Rebecca Chibnall, M. Laurin Council, Carrie Heffington, Friederike Kreisel, David J. Margolis, David Sheinbein, Paola LovatoEric Vivier, Marina Cella, Marco Colonna, Wayne M. Yokoyama, Eugene M. Oltz, Todd A. Fehniger, Brian S. Kim

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish
Article numberaay1005
JournalScience translational medicine
Volume12
Issue number532
DOIs
StatePublished - Feb 26 2020

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