Blood natural killer cell deficiency reveals an immunotherapy strategy for atopic dermatitis.
Journal
Science translational medicine
ISSN: 1946-6242
Titre abrégé: Sci Transl Med
Pays: United States
ID NLM: 101505086
Informations de publication
Date de publication:
26 02 2020
26 02 2020
Historique:
received:
20
05
2019
revised:
12
09
2019
accepted:
31
01
2020
entrez:
28
2
2020
pubmed:
28
2
2020
medline:
24
6
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32102931
pii: 12/532/eaay1005
doi: 10.1126/scitranslmed.aay1005
pmc: PMC7433875
mid: NIHMS1604312
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAMS NIH HHS
ID : K08 AR065577
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR070116
Pays : United States
Organisme : NCI NIH HHS
ID : F32 CA200253
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR056755
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI106697
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA171963
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR027552
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024992
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI102924
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007163
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA091842
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000448
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR070873
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR069062
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002345
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI134035
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA205239
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007317
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK052574
Pays : United States
Organisme : NIH HHS
ID : DP5 OD028125
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Références
Br J Dermatol. 2018 Jan;178(1):34-60
pubmed: 29357600
Trends Immunol. 2010 Nov;31(11):401-6
pubmed: 20829113
J Clin Cell Immunol. 2011 Aug 10;2(3):
pubmed: 21994899
J Immunol. 2017 Apr 15;198(8):3336-3344
pubmed: 28275135
Immunity. 2018 Sep 18;49(3):464-476.e4
pubmed: 30193847
J Exp Med. 2000 Mar 6;191(5):771-80
pubmed: 10704459
Nat Rev Immunol. 2011 Sep 23;11(10):658-71
pubmed: 21941294
Blood. 2010 Nov 11;116(19):3853-64
pubmed: 20696944
J Allergy Clin Immunol. 2013 Oct;132(4):789-801; quiz 788
pubmed: 24075190
J Allergy Clin Immunol. 2003 Dec;112(6 Suppl):S118-27
pubmed: 14657842
J Am Acad Dermatol. 2019 Nov;81(5):1223-1224
pubmed: 31238084
Bioinformatics. 2012 Aug 15;28(16):2184-5
pubmed: 22743226
Int Arch Allergy Appl Immunol. 1990;92(3):318-22
pubmed: 1703517
Immunity. 2015 Jul 21;43(1):161-74
pubmed: 26092469
Lancet Oncol. 2018 May;19(5):694-704
pubmed: 29628312
Clin Rev Allergy Immunol. 2011 Dec;41(3):298-310
pubmed: 21249468
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Curr Protoc Immunol. 2018 Jun 29;:e55
pubmed: 29957859
JAMA Dermatol. 2017 May 1;153(5):406-412
pubmed: 28249066
Gene. 2013 Sep 25;527(2):594-600
pubmed: 23831511
J Exp Med. 2013 Dec 16;210(13):2939-50
pubmed: 24323357
J Allergy Clin Immunol. 2002 Sep;110(3):357-65
pubmed: 12209080
Cell. 2018 Dec 13;175(7):1731-1743.e13
pubmed: 30503213
Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18324-9
pubmed: 22021440
Am J Hum Genet. 2015 Oct 1;97(4):593-607
pubmed: 26430804
J Invest Dermatol. 2014 Jun;134(6):1527-1534
pubmed: 24166134
Nat Rev Immunol. 2013 Feb;13(2):145-9
pubmed: 23348417
Int Immunol. 2012 Dec;24(12):793-802
pubmed: 22962434
J Am Acad Dermatol. 2016 Oct;75(4):842-844
pubmed: 27646746
Genome Biol. 2014;15(12):550
pubmed: 25516281
Nat Commun. 2019 Aug 29;10(1):3897
pubmed: 31467285
J Immunol. 2014 Oct 1;193(7):3717-25
pubmed: 25156365
J Clin Invest. 2017 Nov 1;127(11):4042-4058
pubmed: 28972539
J Immunol. 2006 Jun 15;176(12):7736-44
pubmed: 16751421
Clin Immunol. 2008 Jul;128(1):46-56
pubmed: 18495540
J Am Acad Dermatol. 2016 May;74(5):1017-20
pubmed: 27085236
Lancet. 2016 Jan 2;387(10013):40-52
pubmed: 26454361
Nat Methods. 2015 May;12(5):453-7
pubmed: 25822800
Nat Immunol. 2016 Jun;17(6):626-35
pubmed: 27111143
Exp Dermatol. 2001 Feb;10(1):11-8
pubmed: 11168575
Allergy. 2004 Jun;59(6):561-70
pubmed: 15147438
J Immunol. 2010 Nov 15;185(10):6058-67
pubmed: 20944005
J Leukoc Biol. 2018 Apr;103(4):629-641
pubmed: 29350874
Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2886-91
pubmed: 15699323
N Engl J Med. 2014 Jul 10;371(2):130-9
pubmed: 25006719
N Engl J Med. 2016 Dec 15;375(24):2335-2348
pubmed: 27690741
BMC Bioinformatics. 2009 May 27;10:161
pubmed: 19473525
Nat Protoc. 2015 Feb;10(2):316-33
pubmed: 25612231
Cell. 2019 Jan 10;176(1-2):348-360.e12
pubmed: 30595449
Blood. 2013 May 2;121(18):3599-608
pubmed: 23487023
Sci Transl Med. 2015 Jul 22;7(297):297ra115
pubmed: 26203083
Trends Immunol. 2001 Nov;22(11):633-40
pubmed: 11698225
J Immunol. 2015 Sep 1;195(5):2353-64
pubmed: 26216888
J Exp Med. 1995 Jan 1;181(1):339-44
pubmed: 7528771
J Invest Dermatol. 2017 Jan;137(1):26-30
pubmed: 27616422
Cytometry A. 2013 May;83(5):483-94
pubmed: 23512433
Sci Transl Med. 2013 Jan 30;5(170):170ra16
pubmed: 23363980
J Am Acad Dermatol. 2014 Dec;71(6):1218-33
pubmed: 25264237
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Elife. 2014 Jan 01;3:e01659
pubmed: 24714492
J Immunol. 2016 May 1;196(9):3818-27
pubmed: 26994220
Blood. 2018 Jun 7;131(23):2515-2527
pubmed: 29463563
J Invest Dermatol. 2017 Jun;137(6):1375-1377
pubmed: 28202403
Cell. 2017 Sep 21;171(1):217-228.e13
pubmed: 28890086
Immunity. 2015 Mar 17;42(3):443-56
pubmed: 25786176
Nat Immunol. 2013 Jun;14(6):564-73
pubmed: 23603794
Br J Dermatol. 2012 Apr;166(4):789-96
pubmed: 22233261
Sci Transl Med. 2016 Sep 21;8(357):357ra123
pubmed: 27655849
Front Immunol. 2013 Dec 09;4:422
pubmed: 24367364
Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11736-41
pubmed: 16880407
Eur J Immunol. 2013 May;43(5):1133-41
pubmed: 23552990
Nat Immunol. 2016 Jan;17(1):76-86
pubmed: 26595888