Single-cell analysis reveals differences among iNKT cells colonizing peripheral organs and identifies Klf2 as a key gene for iNKT emigration.
Journal
Cell discovery
ISSN: 2056-5968
Titre abrégé: Cell Discov
Pays: England
ID NLM: 101661034
Informations de publication
Date de publication:
02 Aug 2022
02 Aug 2022
Historique:
received:
16
05
2021
accepted:
02
06
2022
entrez:
1
8
2022
pubmed:
2
8
2022
medline:
2
8
2022
Statut:
epublish
Résumé
Invariant natural killer T cell (iNKT) subsets are differentially distributed in various immune organs. However, it remains unclear whether iNKT cells exhibit phenotypical and functional differences in different peripheral organs and how thymic iNKT cells emigrate to peripheral organs. Here, we used single-cell RNA-seq to map iNKT cells from peripheral organs. iNKT1 cells from liver, spleen, and lymph node appear to have distinct phenotypic profiles and functional capabilities. However, iNKT17 transcriptomes were comparable across peripheral organs. In addition, by integrating data with a thymic iNKT cell study, we uncovered a transient population of recent thymic emigrants, a cluster of peripheral iNKT cells with high expression of transcription factor Kruppel-like factor 2 (Klf2). Deletion of Klf2 led to a severe impairment of iNKT differentiation and migration. Our study revealed that iNKT subsets are uniquely distributed in peripheral organs with some inter-local tissue variation, especially for iNKT1 cell, and identified Klf2 as a rheostat for iNKT cell migration and differentiation.
Identifiants
pubmed: 35915069
doi: 10.1038/s41421-022-00432-z
pii: 10.1038/s41421-022-00432-z
pmc: PMC9343440
doi:
Types de publication
Journal Article
Langues
eng
Pagination
75Subventions
Organisme : Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)
ID : 1R61AR076803-01
Organisme : NIAMS NIH HHS
ID : R61 AR076803
Pays : United States
Organisme : NIAID NIH HHS
ID : R56 AI119041
Pays : United States
Organisme : Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)
ID : 1R56AI119041-01
Organisme : Henry Ford Health System
ID : T71017
Organisme : NIAID NIH HHS
ID : R01 AI119041
Pays : United States
Organisme : Henry Ford Health System
ID : T71016
Organisme : Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)
ID : AI119041-01A1
Informations de copyright
© 2022. The Author(s).
Références
Semin Immunol. 2015 Feb;27(1):26-32
pubmed: 25841627
J Immunother Cancer. 2015 Jan 20;3(1):1
pubmed: 25648675
Elife. 2018 Aug 13;7:
pubmed: 30102153
J Immunol. 2007 Jun 15;178(12):7632-9
pubmed: 17548599
J Exp Med. 2005 Nov 7;202(9):1279-88
pubmed: 16275765
Nat Methods. 2017 Oct;14(10):979-982
pubmed: 28825705
J Exp Med. 2000 Jun 5;191(11):1895-903
pubmed: 10839805
Dev Cell. 2006 Dec;11(6):845-57
pubmed: 17141159
Front Immunol. 2015 May 20;6:240
pubmed: 26042123
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
J Immunol. 2019 Dec 15;203(12):3256-3267
pubmed: 31748350
Nat Immunol. 2008 Mar;9(3):292-300
pubmed: 18246069
J Immunol. 2003 Sep 15;171(6):2960-9
pubmed: 12960320
Immunity. 2015 Sep 15;43(3):566-78
pubmed: 26362265
Nat Rev Immunol. 2011 Feb;11(2):131-42
pubmed: 21267014
J Exp Med. 2000 Sep 4;192(5):741-54
pubmed: 10974039
J Exp Med. 2011 Jun 6;208(6):1179-88
pubmed: 21624939
Front Immunol. 2015 May 27;6:255
pubmed: 26074921
Annu Rev Immunol. 2007;25:297-336
pubmed: 17150027
Front Cell Dev Biol. 2020 May 26;8:384
pubmed: 32528956
Int J Mol Sci. 2018 Feb 01;19(2):
pubmed: 29389901
J Immunol. 2005 Sep 15;175(6):3762-8
pubmed: 16148122
Immunol Rev. 2010 Nov;238(1):195-215
pubmed: 20969594
J Immunol. 2003 Dec 1;171(11):5913-20
pubmed: 14634102
Nat Rev Immunol. 2018 Sep;18(9):559-574
pubmed: 29967365
Nat Immunol. 2016 Jun;17(6):728-39
pubmed: 27089380
Nature. 2005 Mar 24;434(7032):525-9
pubmed: 15791258
Nature. 2006 Jul 20;442(7100):299-302
pubmed: 16855590
Nat Immunol. 2010 Aug;11(8):709-16
pubmed: 20601952
J Exp Med. 2005 Dec 19;202(12):1623-6
pubmed: 16365145
Nature. 2005 Mar 24;434(7032):520-5
pubmed: 15791257
Nature. 2017 Dec 14;552(7684):253-257
pubmed: 29211713
J Immunol. 2010 Jun 1;184(11):6060-6
pubmed: 20427763
Nat Biotechnol. 2014 Apr;32(4):381-386
pubmed: 24658644
Cell. 2019 Jun 13;177(7):1888-1902.e21
pubmed: 31178118
Immunology. 2014 Jul;142(3):321-36
pubmed: 24428389
Nature. 2019 Feb;566(7745):496-502
pubmed: 30787437
J Immunol. 2001 Aug 1;167(3):1164-73
pubmed: 11466330
Science. 2016 Apr 8;352(6282):189-96
pubmed: 27124452
Immunology. 2012 Jul;136(3):273-82
pubmed: 22671023
Nat Commun. 2017 Jan 16;8:14049
pubmed: 28091601