| Literature DB >> 32102931 |
Madison R Mack1,2, Jonathan R Brestoff3, Melissa M Berrien-Elliott4, Anna M Trier1,2, Ting-Lin B Yang1,2, Matthew McCullen3, Patrick L Collins3, Haixia Niu1,2, Nancy D Bodet1,2, Julia A Wagner4, Eugene Park5, Amy Z Xu1,2,6, Fang Wang1,2, Rebecca Chibnall2, M Laurin Council2, Carrie Heffington7, Friederike Kreisel3, David J Margolis8, David Sheinbein2, Paola Lovato9, Eric Vivier10,11, Marina Cella3, Marco Colonna3, Wayne M Yokoyama5, Eugene M Oltz12, Todd A Fehniger4, Brian S Kim13,2,3.
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.Entities:
Year: 2020 PMID： 32102931 PMCID： PMC7433875 DOI： 10.1126/scitranslmed.aay1005
Source DB: PubMed Journal: Sci Transl Med ISSN： 1946-6234 Impact factor: 17.956