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

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 LovatoEric Vivier, Marina Cella, Marco Colonna, Wayne M. Yokoyama, Eugene M. Oltz, Todd A. Fehniger, Brian S. Kim

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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.

Original language	English
Article number	aay1005
Journal	Science translational medicine
Volume	12
Issue number	532
DOIs	https://doi.org/10.1126/scitranslmed.aay1005
State	Published - Feb 26 2020

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Mack, M. R., Brestoff, J. R., Berrien-Elliott, M. M., Trier, A. M., Yang, T. L. B., McCullen, M., Collins, P. L., Niu, H., Bodet, N. D., Wagner, J. A., Park, E., Xu, A. Z., Wang, F., Chibnall, R., Council, M. L., Heffington, C., Kreisel, F., Margolis, D. J., Sheinbein, D., ... Kim, B. S. (2020). Blood natural killer cell deficiency reveals an immunotherapy strategy for atopic dermatitis. Science translational medicine, 12(532), Article aay1005. https://doi.org/10.1126/scitranslmed.aay1005

@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 = "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",

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Mack, MR, Brestoff, JR, Berrien-Elliott, MM, Trier, AM, Yang, TLB, McCullen, M, Collins, PL, Niu, H, Bodet, ND, Wagner, JA, Park, E, Xu, AZ, Wang, F, Chibnall, R, Council, ML, Heffington, C, Kreisel, F, Margolis, DJ, Sheinbein, D, Lovato, P, Vivier, E, Cella, M , Colonna, M , Yokoyama, WM, Oltz, EM, Fehniger, TA & Kim, BS 2020, 'Blood natural killer cell deficiency reveals an immunotherapy strategy for atopic dermatitis', Science translational medicine, vol. 12, no. 532, aay1005. https://doi.org/10.1126/scitranslmed.aay1005

TY - JOUR

T1 - Blood natural killer cell deficiency reveals an immunotherapy strategy for atopic dermatitis

AU - Mack, Madison R.

AU - Brestoff, Jonathan R.

AU - Berrien-Elliott, Melissa M.

AU - Trier, Anna M.

AU - Yang, Ting Lin B.

AU - McCullen, Matthew

AU - Collins, Patrick L.

AU - Niu, Haixia

AU - Bodet, Nancy D.

AU - Wagner, Julia A.

AU - Park, Eugene

AU - Xu, Amy Z.

AU - Wang, Fang

AU - Chibnall, Rebecca

AU - Council, M. Laurin

AU - Heffington, Carrie

AU - Kreisel, Friederike

AU - Margolis, David J.

AU - Sheinbein, David

AU - Lovato, Paola

AU - Vivier, Eric

AU - Cella, Marina

AU - Colonna, Marco

AU - Yokoyama, Wayne M.

AU - Oltz, Eugene M.

AU - Fehniger, Todd A.

AU - Kim, Brian S.

PY - 2020/2/26

Y1 - 2020/2/26

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85080033400&partnerID=8YFLogxK

U2 - 10.1126/scitranslmed.aay1005

DO - 10.1126/scitranslmed.aay1005

M3 - Article

C2 - 32102931

AN - SCOPUS:85080033400

SN - 1946-6234

VL - 12

JO - Science translational medicine

JF - Science translational medicine

IS - 532

M1 - aay1005

ER -

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

Abstract

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