Unique expansion of IL-21+ Tfh and Tph cells under control of ICOS identifies Sjögren's syndrome with ectopic germinal centres and MALT lymphoma.
Adult
Aged
Choristoma
/ etiology
Female
Germinal Center
Humans
Immunophenotyping
Inducible T-Cell Co-Stimulator Protein
/ immunology
Interleukins
/ immunology
Lymphoma, B-Cell, Marginal Zone
/ etiology
Male
Middle Aged
Salivary Gland Diseases
/ immunology
Sjogren's Syndrome
/ complications
T Follicular Helper Cells
/ immunology
T-Lymphocytes, Helper-Inducer
/ immunology
autoimmune diseases
cytokines
sjogren's syndrome
t-lymphocyte subsets
Journal
Annals of the rheumatic diseases
ISSN: 1468-2060
Titre abrégé: Ann Rheum Dis
Pays: England
ID NLM: 0372355
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
16
04
2020
revised:
28
06
2020
accepted:
13
07
2020
pubmed:
24
9
2020
medline:
15
12
2020
entrez:
23
9
2020
Statut:
ppublish
Résumé
To explore the relevance of T-follicular-helper (Tfh) and pathogenic peripheral-helper T-cells (Tph) in promoting ectopic lymphoid structures (ELS) and B-cell mucosa-associated lymphoid tissue (MALT) lymphomas (MALT-L) in Sjögren's syndrome (SS) patients. Salivary gland (SG) biopsies with matched peripheral blood were collected from four centres across the European Union. Transcriptomic (microarray and quantitative PCR) analysis, FACS T-cell immunophenotyping with intracellular cytokine detection, multicolor immune-fluorescence microscopy and Transcriptomic analysis in SG identified Tfh-signature, interleukin-21 (IL-21) and the inducible T-cell co-stimulator (ICOS) costimulatory pathway as the most upregulated genes in ELS+SS patients, with parotid MALT-L displaying a 400-folds increase in IL-21 mRNA. Peripheral CD4 Overall, these findings highlight Tfh and Tph-cells, IL-21 and the ICOS costimulatory pathway as key pathogenic players in SS immunopathology and exploitable therapeutic targets in SS.
Identifiants
pubmed: 32963045
pii: annrheumdis-2020-217646
doi: 10.1136/annrheumdis-2020-217646
pmc: PMC7677495
doi:
Substances chimiques
ICOS protein, human
0
Inducible T-Cell Co-Stimulator Protein
0
Interleukins
0
interleukin-21
MKM3CA6LT1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1588-1599Subventions
Organisme : Versus Arthritis
ID : 21268
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K020250/1
Pays : United Kingdom
Organisme : Versus Arthritis
ID : 21753
Pays : United Kingdom
Organisme : Department of Health
ID : TRF-2018-11-ST2-002
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N003063/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N003063/1
Pays : United Kingdom
Organisme : Versus Arthritis
ID : 20089
Pays : United Kingdom
Informations de copyright
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: BF: Consultancy for Novartis, Roche, and BMS. SJB: Consultancy for Astrazeneca, Biogen, BMS, Celgene, Medimmune, MTPharma, Novartis, Ono, UCB, xtlbio. MB: consultancy and/or unrestricted grant support from Medimmune, GSK, Janssen, UCB. GC and JC are AstraZeneca employees and own company stocks.
Références
Blood. 2007 Apr 15;109(8):3500-4
pubmed: 17197434
Arthritis Res Ther. 2006;8(3):R62
pubmed: 16563187
Front Immunol. 2018 Jul 23;9:1707
pubmed: 30083164
Arthritis Rheum. 2008 Nov;58(11):3377-87
pubmed: 18975336
J Autoimmun. 2010 Jun;34(4):400-7
pubmed: 19889514
Arthritis Rheumatol. 2018 Aug;70(8):1354-1355
pubmed: 29534333
Ann Rheum Dis. 2002 Jun;61(6):554-8
pubmed: 12006334
Immunity. 2019 May 21;50(5):1132-1148
pubmed: 31117010
Nat Rev Rheumatol. 2015 Jun;11(6):368-74
pubmed: 25584898
Clin Immunol. 2013 May;147(2):95-104
pubmed: 23578551
Immunity. 2008 Jul 18;29(1):138-49
pubmed: 18599325
Arthritis Rheumatol. 2017 Sep;69(9):1850-1861
pubmed: 28564491
Leukemia. 2010 Jun;24(6):1186-96
pubmed: 20428202
Am J Pathol. 1997 May;150(5):1583-93
pubmed: 9137085
Front Immunol. 2018 Jul 17;9:1637
pubmed: 30065726
Clin Exp Immunol. 2016 Jan;183(1):76-89
pubmed: 26358223
J Exp Med. 2010 Feb 15;207(2):365-78
pubmed: 20142430
Immunol Cell Biol. 2014 Jan;92(1):64-71
pubmed: 24145858
Rheumatology (Oxford). 2019 Mar 05;:
pubmed: 30838413
Arthritis Rheumatol. 2014 Sep;66(9):2545-57
pubmed: 24891330
J Immunol. 2014 Apr 1;192(7):3166-79
pubmed: 24610013
J Immunol. 2007 Oct 1;179(7):4929-38
pubmed: 17878393
J Immunol. 2007 Jan 15;178(2):817-28
pubmed: 17202343
Arthritis Rheum. 2002 Aug;46(8):2160-71
pubmed: 12209521
Annu Rev Immunol. 2011;29:621-63
pubmed: 21314428
Int J Clin Exp Pathol. 2014 Apr 15;7(5):1988-96
pubmed: 24966908
Front Immunol. 2016 Aug 10;7:304
pubmed: 27559335
Arthritis Rheum. 2005 Jun;52(6):1773-84
pubmed: 15934082
Immunity. 2011 Dec 23;35(6):986-96
pubmed: 22177922
Nature. 2017 Feb 1;542(7639):110-114
pubmed: 28150777
Arthritis Rheumatol. 2018 Feb;70(2):298-307
pubmed: 29073352
Science. 2009 Aug 21;325(5943):1006-10
pubmed: 19608860
Hum Immunol. 2008 Jul;69(7):399-408
pubmed: 18638655
Immunity. 2011 Jun 24;34(6):932-46
pubmed: 21636296
Immunity. 2013 Oct 17;39(4):770-81
pubmed: 24138884
Arthritis Rheumatol. 2016 Apr;68(4):977-85
pubmed: 26606524
Nat Rev Rheumatol. 2017 Mar;13(3):141-154
pubmed: 28202919
J Clin Invest. 2012 Sep;122(9):3059-62
pubmed: 22922252
Nat Rev Rheumatol. 2019 Aug;15(8):475-490
pubmed: 31289377
Nat Immunol. 2011 Jun 12;12(7):639-46
pubmed: 21666689
Blood. 2013 Dec 12;122(25):4068-76
pubmed: 24159176
Immunity. 2009 Sep 18;31(3):457-68
pubmed: 19631565
J Exp Med. 2000 Dec 4;192(11):1545-52
pubmed: 11104797
J Exp Med. 2010 Jan 18;207(1):155-71
pubmed: 20048285
J Exp Med. 2010 Feb 15;207(2):353-63
pubmed: 20142429
J Autoimmun. 2014 Jun;51:57-66
pubmed: 24411167
BMC Bioinformatics. 2013 Jan 16;14:7
pubmed: 23323831
Scand J Immunol. 2018 Jun 8;:e12679
pubmed: 29882349
N Engl J Med. 2018 Mar 08;378(10):931-939
pubmed: 29514034