Blood natural killer cell deficiency reveals an immunotherapy strategy for atopic dermatitis
- 26 February 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Translational Medicine
- Vol. 12 (532)
- https://doi.org/10.1126/scitranslmed.aay1005
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.Funding Information
- Howard Hughes Medical Institute
- National Heart, Lung, and Blood Institute (T32HL00708843)
- NIH Office of the Director (DP5 OD028125)
- National Cancer Institute (F32CA200253)
- National Cancer Institute (R01CA205239)
- National Institute of Allergy and Infectious Diseases (T32AI716339)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK052574)
- National Center for Research Resources (UL1TR000448)
- National Center for Research Resources (1S10RR027552)
- National Center for Research Resources (UL1RR024992)
- National Institute of Allergy and Infectious Diseases (R01AI134035)
- Burroughs Wellcome Fund (AMS 1019648)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR070116)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (K08AR065577)
- National Institute of Allergy and Infectious Diseases (R01AI102924)
- National Institute of Allergy and Infectious Diseases (R01AI134035)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR069062)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR070873)
- H2020 European Research Council (694502)
- Agence Nationale de la Recherche (ANR-17-RHUS-0007)
- MSDAVENIR
- Innate Pharma
- Equipe Labellisée Ligue Nationale contre le Cancer
- Children’s Discovery Institute (MI-F-2019-795)
- Doris Duke Charitable Foundation
- American Skin Association
- LEO Pharma Research Foundation
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