@article{4562e220798442db90e61a64ce5a7a1a,
title = "Blood natural killer cell deficiency reveals an immunotherapy strategy for atopic dermatitis",
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.",
author = "Mack, {Madison R.} and Brestoff, {Jonathan R.} and Berrien-Elliott, {Melissa M.} and Trier, {Anna M.} and Yang, {Ting Lin B.} and Matthew McCullen and Collins, {Patrick L.} and Haixia Niu and Bodet, {Nancy D.} and Wagner, {Julia A.} and Eugene Park and Xu, {Amy Z.} and Fang Wang and Rebecca Chibnall and Council, {M. Laurin} and Carrie Heffington and Friederike Kreisel and Margolis, {David J.} and David Sheinbein and Paola Lovato and Eric Vivier and Marina Cella and Marco Colonna and Yokoyama, {Wayne M.} and Oltz, {Eugene M.} and Fehniger, {Todd A.} and Kim, {Brian S.}",
note = "Funding Information: We thank the Alvin J. Siteman Cancer Center at WUSM; BJH in St. Louis, MO; and the ICTS at WUSM for the use of the Tissue Procurement Core, which provided human biospecimen storage service. We also thank the Siteman Cancer Center and ICTS for the use of the IML, which provided CyTOF services. The Siteman Cancer Center is supported, in part, by National Cancer Institute (NCI) Cancer Center Support Grant P30 CA091842, and the ICTS is funded by the NIH{\textquoteright}s National Center for Advancing Translational Sciences (NCATS) Clinical and Translational Science Award (CTSA) program grant UL1TR002345. We thank the GTAC, which provided sequencing service and is supported by NCI grant P30CA91842 and by ICTS Clinical and Translational Science Award UL1TR000448 from the National Center for Research Resources (NCRR). The Alafi Neuroimaging Laboratory is supported by NCRR Shared Instrumentation grant 1S10RR027552. The DDRCC is supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant P30DK052574. This publication was also made possible, in part, by UL1RR024992 from the NIH NCRR and NIH CTSA grant UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS). B.S.K. was supported by grants from the NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (R01AR070116 and K08AR065577), the Doris Duke Charitable Foundation, the American Skin Association, and LEO Pharma. M.R.M. and A.M.T. were supported by NIH National Institute of Allergy and Infectious Diseases (NIAID) training grant T32AI716339. A.M.T. was also supported by NIH National Heart, Lung, and Blood Institute (NHLBI) training grant T32HL007317. A.Z.X. was supported by the Howard Hughes Medical Institute (HHMI) Medical Fellows Program. The Vivier laboratory at CIML and Assistance-Publique des H{\^o}pitaux de Marseille is supported by funding from the European Research Council (ERC) under the European Union{\textquoteright}s Horizon 2020 research and innovation program (grant agreement no. 694502; TILC), the Agence Nationale de la Recherche including the PIONEER Project (ANR-17-RHUS-0007), Equipe Labellis{\'e}e “La Ligue” (Ligue Nationale contre le Cancer), MSDAVENIR, Innate Pharma, and institutional grants to CIML (INSERM, CNRS, and Aix-Marseille University) and to Marseille Immunopole. J.R.B. was supported by the Children{\textquoteright}s Discovery Institute (MI-F-2019-795), Burroughs Wellcome Fund (CAMS 1019648), and NIH Office of the Director (DP5 OD028125). M.M.B.-E. was supported by NCI F32CA200253 and NIH NHLBI T32HL00708843. T.A.F. was supported by NIH NIAID R01AI102924 and NCI R01CA205239. E.M.O. and M. Colonna were supported by NIH NIAID R01AI134035. D.J.M. was supported by NIH NIAMS R01AR069062 and NIH NIAMS R01AR070873. Publisher Copyright: Copyright {\textcopyright} 2020 The Authors, some rights reserved.",
year = "2020",
month = feb,
day = "26",
doi = "10.1126/scitranslmed.aay1005",
language = "English",
volume = "12",
journal = "Science translational medicine",
issn = "1946-6234",
number = "532",
}