Your browser doesn't support javascript.
loading
Blood natural killer cell deficiency reveals an immunotherapy strategy for atopic dermatitis.
Mack, Madison R; Brestoff, Jonathan R; Berrien-Elliott, Melissa M; Trier, Anna M; Yang, Ting-Lin B; McCullen, Matthew; Collins, Patrick L; Niu, Haixia; Bodet, Nancy D; Wagner, Julia A; Park, Eugene; Xu, Amy Z; Wang, Fang; Chibnall, Rebecca; Council, M Laurin; Heffington, Carrie; Kreisel, Friederike; Margolis, David J; Sheinbein, David; Lovato, Paola; Vivier, Eric; Cella, Marina; Colonna, Marco; Yokoyama, Wayne M; Oltz, Eugene M; Fehniger, Todd A; Kim, Brian S.
Afiliação
  • Mack MR; Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Brestoff JR; Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Berrien-Elliott MM; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Trier AM; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Yang TB; Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • McCullen M; Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Collins PL; Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Niu H; Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Bodet ND; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Wagner JA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Park E; Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Xu AZ; Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Wang F; Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Chibnall R; Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Council ML; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Heffington C; Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Kreisel F; Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Margolis DJ; Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Sheinbein D; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
  • Lovato P; Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Vivier E; Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Cella M; Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Colonna M; Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Yokoyama WM; Barnes-Jewish Hospital, St. Louis, MO 63110, USA.
  • Oltz EM; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Fehniger TA; Department of Dermatology and Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • Kim BS; Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Sci Transl Med ; 12(532)2020 02 26.
Article em En | MEDLINE | ID: mdl-32102931
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Dermatite Atópica / Deficiência de GATA2 Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Dermatite Atópica / Deficiência de GATA2 Idioma: En Ano de publicação: 2020 Tipo de documento: Article