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 Lovato; Eric Vivier; Marina Cella; Marco Colonna; Wayne M. Yokoyama; Eugene M. Oltz; Todd A. Fehniger; Brian S. Kim

doi:10.1126/scitranslmed.aay1005

Research ArticleATOPY

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

View ORCID ProfileMadison R. Mack ¹,²,
View ORCID ProfileJonathan R. Brestoff ³,
View ORCID ProfileMelissa M. Berrien-Elliott ⁴,
View ORCID ProfileAnna M. Trier¹,²,
View ORCID ProfileTing-Lin B. Yang¹,²,
View ORCID ProfileMatthew McCullen³,
View ORCID ProfilePatrick L. Collins³,
Haixia Niu¹,²,
Nancy D. Bodet¹,²,
Julia A. Wagner⁴,
View ORCID ProfileEugene Park⁵,
Amy Z. Xu ¹,²,⁶,
Fang Wang¹,²,
Rebecca Chibnall²,
View ORCID ProfileM. Laurin Council²,
Carrie Heffington⁷,
Friederike Kreisel³,
David J. Margolis ⁸,
View ORCID ProfileDavid Sheinbein²,
View ORCID ProfilePaola Lovato⁹,
View ORCID ProfileEric Vivier ¹⁰,¹¹,
View ORCID ProfileMarina Cella³,
View ORCID ProfileMarco Colonna ³,
View ORCID ProfileWayne M. Yokoyama⁵,
Eugene M. Oltz ¹²,
View ORCID ProfileTodd A. Fehniger ⁴ and
View ORCID ProfileBrian S. Kim ¹,²,³,*

¹Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
²Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
³Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
⁴Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
⁵Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
⁶Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
⁷Barnes-Jewish Hospital, St. Louis, MO 63110, USA.
⁸Department of Dermatology and Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, Philadelphia, PA 19104, USA.
⁹Skin Research, LEO Pharma A/S, Industriparken 55, Ballerup, Denmark.
¹⁰Aix Marseille University, APHM, CNRS, INSERM, CIML, Hôpital de la Timone, Marseille-Immunopole, Marseille, France.
¹¹Innate Pharma Research Laboratories, Innate Pharma, Marseille, France.
¹²Department of Microbial Infection and Immunity, Ohio State University, Wexner School of Medicine, Columbus, OH 43210, USA.

↵*Corresponding author. Email: briankim{at}wustl.edu

See allHide authors and affiliations

Science Translational Medicine 26 Feb 2020:
Vol. 12, Issue 532, eaay1005
DOI: 10.1126/scitranslmed.aay1005

Madison R. Mack

1Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.

2Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Madison R. Mack

Jonathan R. Brestoff

3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Jonathan R. Brestoff

Melissa M. Berrien-Elliott

4Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Melissa M. Berrien-Elliott

Anna M. Trier

1Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.

2Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Anna M. Trier

Ting-Lin B. Yang

1Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.

2Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Ting-Lin B. Yang

Matthew McCullen

3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Matthew McCullen

Patrick L. Collins

3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Patrick L. Collins

Haixia Niu

1Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.

2Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Nancy D. Bodet

1Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.

2Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Julia A. Wagner

4Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Eugene Park

5Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Eugene Park

Amy Z. Xu

1Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.

2Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

6Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Fang Wang

1Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.

2Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Rebecca Chibnall

2Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

M. Laurin Council

2Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for M. Laurin Council

Carrie Heffington

7Barnes-Jewish Hospital, St. Louis, MO 63110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Friederike Kreisel

3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

David J. Margolis

8Department of Dermatology and Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

David Sheinbein

2Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for David Sheinbein

Paola Lovato

9Skin Research, LEO Pharma A/S, Industriparken 55, Ballerup, Denmark.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Paola Lovato

Eric Vivier

10Aix Marseille University, APHM, CNRS, INSERM, CIML, Hôpital de la Timone, Marseille-Immunopole, Marseille, France.

11Innate Pharma Research Laboratories, Innate Pharma, Marseille, France.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Eric Vivier

Marina Cella

3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Marina Cella

Marco Colonna

3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Marco Colonna

Wayne M. Yokoyama

5Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Wayne M. Yokoyama

Eugene M. Oltz

12Department of Microbial Infection and Immunity, Ohio State University, Wexner School of Medicine, Columbus, OH 43210, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Todd A. Fehniger

4Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Todd A. Fehniger

Brian S. Kim

1Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.

2Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Brian S. Kim
For correspondence: briankim@wustl.edu

Article
Figures & Data
Info & Metrics
eLetters
PDF

Nurturing NK cells to treat atopic dermatitis

The skin condition atopic dermatitis (AD) is driven by a type 2 immune response. Mack et al. performed high-dimensional immune profiling of patients with AD and revealed deficiencies in certain subsets of natural killer (NK) cells. NK cells showed signs of activation-induced cell death and were restored in patients that responded to immunotherapy. Circulating NK cells were also decreased in a mouse AD model; boosting NK cells with an IL-15 superagonist ameliorated symptoms in the mice. These results suggest that strategies to restore NK cells could help rebalance immunity in AD.

http://www.sciencemag.org/about/science-licenses-journal-article-reuse

This is an article distributed under the terms of the Science Journals Default License.

View Full Text

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

Nurturing NK cells to treat atopic dermatitis

Science Translational Medicine

Article Tools