A novel unconventional T cell population enriched in Crohn's disease.
Crohn's disease
IBD
T-cell receptor
alpha beta T cells
mucosal immunology
Journal
Gut
ISSN: 1468-3288
Titre abrégé: Gut
Pays: England
ID NLM: 2985108R
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
09
06
2021
accepted:
22
02
2022
pubmed:
11
3
2022
medline:
12
10
2022
entrez:
10
3
2022
Statut:
ppublish
Résumé
One of the current hypotheses to explain the proinflammatory immune response in IBD is a dysregulated T cell reaction to yet unknown intestinal antigens. As such, it may be possible to identify disease-associated T cell clonotypes by analysing the peripheral and intestinal T-cell receptor (TCR) repertoire of patients with IBD and controls. We performed bulk TCR repertoire profiling of both the TCR alpha and beta chains using high-throughput sequencing in peripheral blood samples of a total of 244 patients with IBD and healthy controls as well as from matched blood and intestinal tissue of 59 patients with IBD and disease controls. We further characterised specific T cell clonotypes via single-cell RNAseq. We identified a group of clonotypes, characterised by semi-invariant TCR alpha chains, to be significantly enriched in the blood of patients with Crohn's disease (CD) and particularly expanded in the CD8 We identified and characterised a subpopulation of unconventional Crohn-associated invariant T (CAIT) cells. Multiple evidence suggests these cells to be part of the NKT type II population. The potential implications of this population for CD or a subset thereof remain to be elucidated, and the immunophenotype and antigen reactivity of CAIT cells need further investigations in future studies.
Identifiants
pubmed: 35264446
pii: gutjnl-2021-325373
doi: 10.1136/gutjnl-2021-325373
pmc: PMC9554086
doi:
Substances chimiques
Receptors, Antigen, T-Cell
0
Receptors, Antigen, T-Cell, alpha-beta
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2194-2204Informations de copyright
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: ER, AF, PB and IZM hold a pending patent application based on the results described in this manuscript (EP21217058.3).
Références
J Crohns Colitis. 2017 Jul 01;11(7):831-839
pubmed: 28158397
Cell Discov. 2020 Apr 28;6:22
pubmed: 32351704
Nat Immunol. 2020 Jun;21(6):684-694
pubmed: 32231301
Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13578-83
pubmed: 15342907
Nutrients. 2017 Oct 18;9(10):
pubmed: 29057829
Annu Rev Immunol. 2010;28:573-621
pubmed: 20192811
Mol Immunol. 2021 Feb;130:64-68
pubmed: 33360378
Sci Rep. 2019 May 8;9(1):7094
pubmed: 31068647
Gut. 2019 Nov;68(11):1961-1970
pubmed: 30792246
Immunobiology. 2013 Feb;218(2):213-24
pubmed: 22647874
Nat Commun. 2021 Mar 15;12(1):1669
pubmed: 33723257
Nat Rev Gastroenterol Hepatol. 2015 Dec;12(12):672
pubmed: 26526125
BMC Biotechnol. 2017 Jul 10;17(1):61
pubmed: 28693542
Nat Rev Nephrol. 2021 Dec;17(12):795-813
pubmed: 34446934
Proc Natl Acad Sci U S A. 2021 Aug 24;118(34):
pubmed: 34417291
Gastroenterology. 2017 Nov;153(5):1320-1337.e16
pubmed: 28782508
Nat Rev Endocrinol. 2019 Nov;15(11):635-650
pubmed: 31534209
Nature. 2021 Dec;600(7888):302-307
pubmed: 34759313
Lancet. 1980 Mar 8;1(8167):514
pubmed: 6102236
PLoS Comput Biol. 2017 Jul 6;13(7):e1005572
pubmed: 28683116
Nat Methods. 2019 Dec;16(12):1289-1296
pubmed: 31740819
Hum Mol Genet. 2021 Apr 27;30(5):356-369
pubmed: 33555323
Dig Dis. 2013;31(3-4):310-6
pubmed: 24246980
Inflamm Bowel Dis. 2013 May;19(6):1330-8
pubmed: 23518808
Nat Methods. 2015 May;12(5):380-1
pubmed: 25924071
J Crohns Colitis. 2020 Jul 9;14(6):778-790
pubmed: 31711184
Am J Clin Nutr. 2014 Feb;99(2):369-77
pubmed: 24305680
Aging Cell. 2019 Aug;18(4):e12960
pubmed: 31044512
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
Front Immunol. 2018 Jun 01;9:1212
pubmed: 29910812
Gastroenterology. 2014 May;146(6):1489-99
pubmed: 24560869
Lancet Neurol. 2014 Aug;13(8):807-22
pubmed: 25008549
Nat Commun. 2014 May 15;5:3866
pubmed: 24832684
Nucleic Acids Res. 2018 Jul 2;46(W1):W396-W401
pubmed: 29790966
Nature. 2003 Mar 13;422(6928):164-9
pubmed: 12634786
Inflamm Bowel Dis. 2016 Jun;22(6):1275-85
pubmed: 27135481
Nat Immunol. 2019 Sep;20(9):1110-1128
pubmed: 31406380
Hum Mol Genet. 2019 Jun 15;28(12):2078-2092
pubmed: 30590525
Genome Biol. 2015 Dec 10;16:278
pubmed: 26653891
Pharmacogenomics J. 2014 Apr;14(2):192-200
pubmed: 23712092
Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2012 Jun;55(6-7):831-5
pubmed: 22736164
Nat Immunol. 2015 Nov;16(11):1114-23
pubmed: 26482978
Nat Genet. 2015 Feb;47(2):172-9
pubmed: 25559196
Mucosal Immunol. 2018 Sep;11(5):1487-1495
pubmed: 29988119
Clin Exp Immunol. 2014 May;176(2):266-74
pubmed: 24450998
Nat Methods. 2014 Jun;11(6):653-5
pubmed: 24793455