Single-cell analysis reveals innate lymphoid cell lineage infidelity in atopic dermatitis.
Innate lymphoid cells
atopic dermatitis
human skin
single-cell RNA sequencing
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
13
11
2020
revised:
23
06
2021
accepted:
13
07
2021
pubmed:
8
8
2021
medline:
4
3
2022
entrez:
7
8
2021
Statut:
ppublish
Résumé
Although ample knowledge exists about phenotype and function of cutaneous T lymphocytes, much less is known about the lymphocytic components of the skin's innate immune system. To better understand the biologic role of cutaneous innate lymphoid cells (ILCs), we investigated their phenotypic and molecular features under physiologic (normal human skin [NHS]) and pathologic (lesional skin of patients with atopic dermatitis [AD]) conditions. Skin punch biopsies and reduction sheets as well as blood specimens were obtained from either patients with AD or healthy individuals. Cell and/or tissue samples were analyzed by flow cytometry, immunohistochemistry, and single-cell RNA sequencing or subjected to in vitro/ex vivo culture. Notwithstanding substantial quantitative differences between NHS and AD skin, we found that the vast majority of cutaneous ILCs belong to the CRTH2 These findings support the concept that instead of being a stable entity with well-defined components, the skin immune system consists of a network of highly flexible cellular players that are capable of adjusting their function to the needs and challenges of the environment.
Sections du résumé
BACKGROUND
Although ample knowledge exists about phenotype and function of cutaneous T lymphocytes, much less is known about the lymphocytic components of the skin's innate immune system.
OBJECTIVE
To better understand the biologic role of cutaneous innate lymphoid cells (ILCs), we investigated their phenotypic and molecular features under physiologic (normal human skin [NHS]) and pathologic (lesional skin of patients with atopic dermatitis [AD]) conditions.
METHODS
Skin punch biopsies and reduction sheets as well as blood specimens were obtained from either patients with AD or healthy individuals. Cell and/or tissue samples were analyzed by flow cytometry, immunohistochemistry, and single-cell RNA sequencing or subjected to in vitro/ex vivo culture.
RESULTS
Notwithstanding substantial quantitative differences between NHS and AD skin, we found that the vast majority of cutaneous ILCs belong to the CRTH2
CONCLUSION
These findings support the concept that instead of being a stable entity with well-defined components, the skin immune system consists of a network of highly flexible cellular players that are capable of adjusting their function to the needs and challenges of the environment.
Identifiants
pubmed: 34363841
pii: S0091-6749(21)01198-2
doi: 10.1016/j.jaci.2021.07.025
pmc: PMC9130781
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
624-639Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Références
J Allergy Clin Immunol. 2015 Dec;136(6):1653-1663.e7
pubmed: 26025126
J Am Acad Dermatol. 2019 Aug;81(2):510-519
pubmed: 31009665
J Allergy Clin Immunol. 2016 Nov;138(5):1265-1276
pubmed: 27677386
Nat Commun. 2017 Jan 16;8:14049
pubmed: 28091601
Nat Immunol. 2020 Feb;21(2):106-108
pubmed: 31900463
Blood. 2014 Jul 31;124(5):700-9
pubmed: 24778151
Inflamm Cell Signal. 2016;3(3):
pubmed: 28286805
Nature. 2019 Oct;574(7778):365-371
pubmed: 31597962
Curr Allergy Asthma Rep. 2016 Oct;16(10):73
pubmed: 27645534
Immunity. 2015 Jul 21;43(1):146-60
pubmed: 26187413
Nat Commun. 2020 Nov 5;11(1):5587
pubmed: 33154365
J Allergy Clin Immunol. 2009 Jun;123(6):1244-52.e2
pubmed: 19439349
J Exp Med. 2013 Dec 16;210(13):2939-50
pubmed: 24323357
J Exp Med. 2019 Aug 5;216(8):1726-1727
pubmed: 31337734
J Invest Dermatol. 2014 Sep;134(9):2351-2360
pubmed: 24658504
Nat Immunol. 2011 Sep 11;12(11):1055-62
pubmed: 21909091
Proc Natl Acad Sci U S A. 2013 Aug 20;110(34):13921-6
pubmed: 23918359
Cell. 2017 Mar 9;168(6):1086-1100.e10
pubmed: 28283063
Nat Immunol. 2016 Apr;17(4):451-60
pubmed: 26878113
Nature. 2019 Oct;574(7777):254-258
pubmed: 31534216
Front Immunol. 2019 Feb 08;10:170
pubmed: 30800126
J Immunol. 2014 Oct 1;193(7):3717-25
pubmed: 25156365
J Invest Dermatol. 2014 Apr;134(4):984-991
pubmed: 24352038
J Exp Med. 2019 Aug 5;216(8):1762-1776
pubmed: 31201208
Nat Commun. 2019 May 14;10(1):2162
pubmed: 31089134
Genome Biol. 2018 Feb 6;19(1):15
pubmed: 29409532
Nat Methods. 2019 Dec;16(12):1289-1296
pubmed: 31740819
Trends Immunol. 2020 Feb;41(2):100-112
pubmed: 31948873
J Invest Dermatol. 2016 Feb;136(2):487-496
pubmed: 26802241
Nat Immunol. 2020 Feb;21(2):168-177
pubmed: 31873294
J Allergy Clin Immunol. 2014 Apr;133(4):1184-94
pubmed: 24388011
Gut. 2009 Sep;58(9):1207-17
pubmed: 18483078
Int J Parasitol. 2011 Aug 15;41(10):1069-77
pubmed: 21787777
J Allergy Clin Immunol. 2020 Nov;146(5):1056-1069
pubmed: 32344053
Nat Commun. 2021 Feb 17;12(1):1088
pubmed: 33597522
Blood Adv. 2017 Mar 30;1(10):577-589
pubmed: 29296700
Nature. 2017 Sep 14;549(7671):277-281
pubmed: 28869974
J Immunol. 2016 Jan 1;196(1):45-54
pubmed: 26582946
Nature. 2005 Sep 15;437(7057):369-75
pubmed: 16163348
J Invest Dermatol. 2016 Dec;136(12):2396-2405
pubmed: 27456756
World Allergy Organ J. 2010 Mar;3(3):44-7
pubmed: 23282416
J Invest Dermatol. 2008 Jun;128(6):1460-9
pubmed: 18079745
Cell Res. 2020 Jun;30(6):475-491
pubmed: 32376911
Front Immunol. 2018 Apr 09;9:486
pubmed: 29686665
J Invest Dermatol. 2019 Oct;139(10):2185-2194.e3
pubmed: 31121178
Cell. 2019 Feb 21;176(5):982-997.e16
pubmed: 30712873
J Allergy Clin Immunol Pract. 2020 Jun;8(6):1840-1852
pubmed: 32499033
J Exp Med. 2006 Oct 2;203(10):2271-9
pubmed: 16982811
J Immunol. 2006 Jan 1;176(1):211-6
pubmed: 16365412
J Mol Diagn. 2000 Feb;2(1):5-10
pubmed: 11272902
Front Immunol. 2015 Nov 23;6:597
pubmed: 26635811
Nat Immunol. 2013 Jun;14(6):564-73
pubmed: 23603794
J Histochem Cytochem. 2020 Feb;68(2):127-138
pubmed: 31880187
Genome Biol. 2019 Mar 19;20(1):59
pubmed: 30890159
Nat Commun. 2020 Jan 29;11(1):577
pubmed: 31996669
Nat Immunol. 2019 Aug;20(8):992-1003
pubmed: 31263279
Am J Pathol. 2011 Jun;178(6):2496-503
pubmed: 21641376
J Invest Dermatol. 1996 Dec;107(6):871-6
pubmed: 8941677
J Immunol. 2006 Apr 1;176(7):4331-6
pubmed: 16547270
J Exp Med. 2017 Jan;214(1):27-37
pubmed: 28011865