A single-cell transcriptional gradient in human cutaneous memory T cells restricts Th17/Tc17 identity.
ZFP36
ZFP36L2
cytokine
inflammation
psoriasis
resident-memory T cell
tristetraprolin scRNA-seq
Journal
Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894
Informations de publication
Date de publication:
16 08 2022
16 08 2022
Historique:
received:
04
01
2022
revised:
21
05
2022
accepted:
14
07
2022
entrez:
17
8
2022
pubmed:
18
8
2022
medline:
20
8
2022
Statut:
ppublish
Résumé
The homeostatic mechanisms that fail to restrain chronic tissue inflammation in diseases, such as psoriasis vulgaris, remain incompletely understood. We profiled transcriptomes and epitopes of single psoriatic and normal skin-resident T cells, revealing a gradated transcriptional program of coordinately regulated inflammation-suppressive genes. This program, which is sharply suppressed in lesional skin, strikingly restricts Th17/Tc17 cytokine and other inflammatory mediators on the single-cell level. CRISPR-based deactivation of two core components of this inflammation-suppressive program, ZFP36L2 and ZFP36, replicates the interleukin-17A (IL-17A), granulocyte macrophage-colony-stimulating factor (GM-CSF), and interferon gamma (IFNγ) elevation in psoriatic memory T cells deficient in these transcripts, functionally validating their influence. Combinatoric expression analysis indicates the suppression of specific inflammatory mediators by individual program members. Finally, we find that therapeutic IL-23 blockade reduces Th17/Tc17 cell frequency in lesional skin but fails to normalize this inflammatory-suppressive program, suggesting how treated lesions may be primed for recurrence after withdrawal of treatment.
Identifiants
pubmed: 35977472
pii: S2666-3791(22)00258-0
doi: 10.1016/j.xcrm.2022.100715
pmc: PMC9418858
pii:
doi:
Substances chimiques
Inflammation Mediators
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
100715Subventions
Organisme : NIAMS NIH HHS
ID : T32 AR007175
Pays : United States
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests A.M. is a cofounder of Arsenal Biosciences, Spotlight Therapeutics, and Survey Genomics. A.M. serves on the boards of directors at Spotlight Therapeutics and Survey Genomics and is board observer (and former member of the board of directors) at Arsenal Biosciences. A.M. is a member of the scientific advisory boards of Arsenal Biosciences, Spotlight Therapeutics, Survey Genomics, and NewLimit. A.M. owns stock in Arsenal Biosciences, Spotlight Therapeutics, NewLimit, Survey Genomics, PACT Pharma, and Merck. A.M. has received fees from Arsenal Biosciences, Spotlight Therapeutics, NewLimit, 23andMe, PACT Pharma, Juno Therapeutics, Trizell, Vertex, Merck, Amgen, Genentech, AlphaSights, Rupert Case Management, Bernstein, and ALDA. A.M. is an investor in and informal advisor to Offline Ventures and a client of EPIQ.
Références
J Immunol. 2004 Jun 15;172(12):7263-71
pubmed: 15187101
FEBS Lett. 2012 Jan 2;586(1):41-6
pubmed: 22138182
Nat Methods. 2019 Dec;16(12):1289-1296
pubmed: 31740819
J Allergy Clin Immunol. 2021 Jun;147(6):2370-2380
pubmed: 33309739
Clin Rev Allergy Immunol. 2016 Jun;50(3):377-89
pubmed: 27025861
Eur J Immunol. 2020 Jun;50(6):891-902
pubmed: 32043568
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Front Immunol. 2020 Jun 23;11:1291
pubmed: 32655569
Science. 2021 Jan 22;371(6527):
pubmed: 33479125
J Gen Psychol. 2003 Apr;130(2):149-68
pubmed: 12773018
J Invest Dermatol. 2019 Apr;139(4):878-889
pubmed: 30423328
Nat Immunol. 2019 Feb;20(2):163-172
pubmed: 30643263
Nat Methods. 2017 Jul;14(7):687-690
pubmed: 28581496
Cell. 2019 Aug 22;178(5):1176-1188.e15
pubmed: 31442406
J Immunol. 2000 Aug 15;165(4):1902-9
pubmed: 10925271
Sci Transl Med. 2015 Jan 7;7(269):269rv1
pubmed: 25568072
Nat Biotechnol. 2016 May;34(5):525-7
pubmed: 27043002
Pigment Cell Melanoma Res. 2019 Sep;32(5):612-622
pubmed: 31230406
Nat Biotechnol. 2019 May;37(5):547-554
pubmed: 30936559
CRISPR J. 2022 Feb;5(1):123-130
pubmed: 35119294
Sci Immunol. 2021 Jan 22;6(55):
pubmed: 33483337
Cell Rep. 2018 Oct 23;25(4):871-883
pubmed: 30355494
Immunity. 2020 Oct 13;53(4):878-894.e7
pubmed: 33053333
J Invest Dermatol. 2008 May;128(5):1207-11
pubmed: 18200064
J Exp Med. 2019 May 6;216(5):1170-1181
pubmed: 30910796
Nat Methods. 2017 Oct;14(10):979-982
pubmed: 28825705
Mol Cell Biol. 2010 Oct;30(20):4877-89
pubmed: 20696842
Elife. 2018 May 31;7:
pubmed: 29848443
iScience. 2020 Sep 19;23(10):101582
pubmed: 33205009
Nat Commun. 2020 Apr 14;11(1):1801
pubmed: 32286271
J Invest Dermatol. 2022 Feb;142(2):402-413
pubmed: 34333017
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Genome Biol. 2018 Apr 12;19(1):53
pubmed: 29650040
Nat Commun. 2020 Mar 3;11(1):1169
pubmed: 32127540
Nat Biotechnol. 2014 Apr;32(4):381-386
pubmed: 24658644
Eur J Immunol. 2021 Jan;51(1):115-124
pubmed: 32902872
J Immunol. 2000 Apr 1;164(7):3591-5
pubmed: 10725714
Sci Rep. 2019 Mar 26;9(1):5233
pubmed: 30914743
Science. 2020 Mar 13;367(6483):1255-1260
pubmed: 32165587
Nature. 2019 Feb;566(7745):496-502
pubmed: 30787437
Cell. 2019 Jun 13;177(7):1888-1902.e21
pubmed: 31178118
Nat Commun. 2018 Apr 19;9(1):1558
pubmed: 29674694
J Immunol. 2014 Apr 1;192(7):3111-20
pubmed: 24610014
Eur J Immunol. 1999 Dec;29(12):4081-91
pubmed: 10602019
Trends Immunol. 2009 Dec;30(12):592-602
pubmed: 19879803
Nat Commun. 2020 Nov 30;11(1):6077
pubmed: 33257685
Proc Natl Acad Sci U S A. 2021 May 25;118(21):
pubmed: 34006646
Blood. 2000 Mar 15;95(6):1891-9
pubmed: 10706852
Biol Open. 2018 Mar 12;7(3):
pubmed: 29449217
Biology (Basel). 2021 Jan 19;10(1):
pubmed: 33477783
J Biol Chem. 2009 Apr 24;284(17):11216-23
pubmed: 19258311
Sci Immunol. 2022 Apr 15;7(70):eabl9165
pubmed: 35427179
JCI Insight. 2017 Jun 2;2(11):
pubmed: 28570274
Genome Biol. 2019 Oct 17;20(1):210
pubmed: 31623682
Front Immunol. 2014 Feb 19;5:58
pubmed: 24600449
J Exp Med. 2019 Dec 2;216(12):2748-2762
pubmed: 31558615
Science. 2016 Apr 22;352(6284):453-9
pubmed: 27102483