SLE serum induces altered goblet cell differentiation and leakiness in human intestinal organoids.
Gut Leakiness
Intestinal Homeostasis
Organoids
Systemic Lupus Erythematosus (SLE)
scRNA-seq
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
Mar 2024
Mar 2024
Historique:
received:
04
10
2023
accepted:
05
01
2024
revised:
21
12
2023
medline:
18
3
2024
pubmed:
6
2
2024
entrez:
5
2
2024
Statut:
ppublish
Résumé
Human intestinal epithelial cells are the interface between luminal content and basally residing immune cells. They form a tight monolayer that constantly secretes mucus creating a multilayered protective barrier. Alterations in this barrier can lead to increased permeability which is common in systemic lupus erythematosus (SLE) patients. However, it remains unexplored how the barrier is affected. Here, we present an in vitro model specifically designed to examine the effects of SLE on epithelial cells. We utilize human colon organoids that are stimulated with serum from SLE patients. Combining transcriptomic with functional analyses revealed that SLE serum induced an expression profile marked by a reduction of goblet cell markers and changed mucus composition. In addition, organoids exhibited imbalanced cellular composition along with enhanced permeability, altered mitochondrial function, and an interferon gene signature. Similarly, transcriptomic analysis of SLE colon biopsies revealed a downregulation of secretory markers. Our work uncovers a crucial connection between SLE and intestinal homeostasis that might be promoted in vivo through the blood, offering insights into the causal connection of barrier dysfunction and autoimmune diseases.
Identifiants
pubmed: 38316934
doi: 10.1038/s44321-024-00023-3
pii: 10.1038/s44321-024-00023-3
pmc: PMC10940301
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
547-574Informations de copyright
© 2024. The Author(s).
Références
Proc Natl Acad Sci U S A. 2017 Oct 17;114(42):11027-11033
pubmed: 28973871
Antibiotics (Basel). 2021 Dec 14;10(12):
pubmed: 34943746
Mucosal Immunol. 2015 Jul;8(4):712-9
pubmed: 25872481
Prog Mol Biol Transl Sci. 2010;96:157-73
pubmed: 21075344
Cell Rep. 2016 May 24;15(8):1743-56
pubmed: 27184849
Ann Rheum Dis. 2022 Mar;81(3):379-385
pubmed: 34462261
BMC Genomics. 2018 Jun 19;19(1):477
pubmed: 29914354
Rheumatol Int. 2018 Jun;38(6):1003-1008
pubmed: 29181621
PLoS One. 2013 Jun 24;8(6):e67003
pubmed: 23826184
Mucosal Immunol. 2018 Nov;11(6):1551-1557
pubmed: 29867079
EBioMedicine. 2023 May;91:104567
pubmed: 37062177
Gut. 2015 Oct;64(10):1529-38
pubmed: 25691495
J Cell Mol Med. 2022 Sep;26(17):4710-4720
pubmed: 35946046
J Surg Res. 2000 Sep;93(1):182-96
pubmed: 10945962
J Intern Med. 2019 May;285(5):479-490
pubmed: 30963635
Science. 2021 Apr 16;372(6539):
pubmed: 33859001
Front Immunol. 2021 May 12;12:657363
pubmed: 34054820
J Interferon Cytokine Res. 2011 Oct;31(10):781-9
pubmed: 21787222
Science. 2021 Nov 05;374(6568):eabe6723
pubmed: 34735226
Gut Pathog. 2016 Dec 8;8:64
pubmed: 27980687
Curr Opin Immunol. 2019 Dec;61:80-85
pubmed: 31590039
Proc Natl Acad Sci U S A. 2016 Sep 13;113(37):E5399-407
pubmed: 27573849
Cell Mol Gastroenterol Hepatol. 2022;13(5):1554-1589
pubmed: 35176508
Cell Rep. 2015 Jan 13;10(2):239-52
pubmed: 25558064
Ann N Y Acad Sci. 2022 Aug;1514(1):21-33
pubmed: 35580994
Gastroenterology. 2011 Nov;141(5):1762-72
pubmed: 21889923
Nat Rev Mol Cell Biol. 2021 Jan;22(1):39-53
pubmed: 32958874
Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15064-9
pubmed: 18806221
Gut. 2008 Jun;57(6):764-71
pubmed: 18250125
Med Sci Sports Exerc. 2012 Dec;44(12):2315-21
pubmed: 22776878
Genome Biol. 2014;15(12):550
pubmed: 25516281
Ann Rheum Dis. 2021 Dec;80(12):1575-1583
pubmed: 34426398
Bioinformatics. 2011 Jun 15;27(12):1739-40
pubmed: 21546393
Nat Commun. 2021 Mar 31;12(1):1980
pubmed: 33790300
Immunol Cell Biol. 2017 Oct;95(9):824-831
pubmed: 28649995
Nat Rev Gastroenterol Hepatol. 2023 Jul;20(7):417-432
pubmed: 37186118
Cell Mol Gastroenterol Hepatol. 2022;13(1):219-232
pubmed: 34418586
Proc Natl Acad Sci U S A. 2019 Dec 3;116(49):24819-24829
pubmed: 31740620
Cell Mol Gastroenterol Hepatol. 2023;15(4):971-984
pubmed: 36414210
Appl Environ Microbiol. 2018 Jan 31;84(4):
pubmed: 29196292
Lupus. 2017 Aug;26(9):937-943
pubmed: 28420044
Nature. 2017 Mar 16;543(7645):424-427
pubmed: 28273069
JCI Insight. 2018 Sep 6;3(17):
pubmed: 30185674
Cell. 2021 Jun 24;184(13):3573-3587.e29
pubmed: 34062119
Scand J Gastroenterol. 2014 Jun;49(6):681-9
pubmed: 24694282
Science. 2020 Aug 7;369(6504):712-717
pubmed: 32527928
J Immunol. 2014 Jun 15;192(12):5459-68
pubmed: 24907379
Science. 2023 Jan 13;379(6628):127-128
pubmed: 36634170
J Biomed Biotechnol. 2011;2011:432595
pubmed: 22028588
Gastroenterology. 2020 Oct;159(4):1564-1567
pubmed: 32474118
Bioinformatics. 2020 Feb 15;36(4):1307-1308
pubmed: 31498385
ERJ Open Res. 2021 Dec 13;7(4):
pubmed: 34912883
Front Immunol. 2022 Jul 22;13:863317
pubmed: 35936008
Trends Immunol. 2018 Sep;39(9):677-696
pubmed: 29716793
Front Med (Lausanne). 2022 Jun 30;9:915179
pubmed: 35847775
Curr Protoc Immunol. 2020 Dec;131(1):e112
pubmed: 33175441
Mediators Inflamm. 2015;2015:659018
pubmed: 26770020
Ann Rheum Dis. 2019 Jul;78(7):947-956
pubmed: 30782585
J Interferon Cytokine Res. 2018 Apr;38(4):171-185
pubmed: 29638206
Int J Pharm. 2017 Oct 30;532(1):555-572
pubmed: 28917986
Sci Rep. 2019 Mar 14;9(1):4530
pubmed: 30872710
Clin Sci (Lond). 2019 Apr 15;133(7):821-838
pubmed: 30872359
Nat Rev Gastroenterol Hepatol. 2019 Jan;16(1):19-34
pubmed: 30429586
Nat Rev Gastroenterol Hepatol. 2018 Aug;15(8):497-516
pubmed: 29844587
Nature. 2019 Mar;567(7746):49-55
pubmed: 30814735
Nat Rev Rheumatol. 2023 Jun;19(6):331-342
pubmed: 37041269
Nature. 2016 Jun 15;534(7607):335-40
pubmed: 27306184
Sci Rep. 2012;2:568
pubmed: 22891156
Oncol Rep. 2006 Oct;16(4):663-70
pubmed: 16969477
Gut. 1994 Mar;35(3):353-9
pubmed: 8150346
Appl Environ Microbiol. 2014 Dec;80(24):7551-60
pubmed: 25261516
J Am Soc Nephrol. 2007 Aug;18(8):2350-8
pubmed: 17625118
Nat Commun. 2021 Jan 11;12(1):262
pubmed: 33431859
Cytokine. 2011 Jan;53(1):74-83
pubmed: 20926308
Front Immunol. 2023 Jun 08;14:1211336
pubmed: 37359538
PLoS One. 2014 May 05;9(5):e93846
pubmed: 24796678
Front Immunol. 2012 Oct 09;3:310
pubmed: 23087688
Arthritis Res Ther. 2010;12 Suppl 1:S6
pubmed: 20392292
Trends Biotechnol. 2019 Jul;37(7):744-760
pubmed: 30591184
Gut. 2019 Dec;68(12):2142-2151
pubmed: 30914450
Lancet. 2001 Mar 31;357(9261):1027-32
pubmed: 11293608
Arthritis Res Ther. 2019 Apr 29;21(1):107
pubmed: 31036046
Clin Exp Immunol. 1994 Apr;96(1):15-9
pubmed: 7512005
J Proteome Res. 2010 Jun 4;9(6):3108-17
pubmed: 20423149
STAR Protoc. 2021 Mar 18;2(1):100386
pubmed: 33778780
Cell Stem Cell. 2018 Dec 6;23(6):787-793.e6
pubmed: 30526881
Cell Death Discov. 2020 May 4;6:33
pubmed: 32377396
Gut. 2017 Dec;66(12):2069-2079
pubmed: 27803115
Annu Rev Immunol. 2017 Apr 26;35:119-147
pubmed: 28125357
Physiol Genomics. 2012 Dec 18;44(24):1165-78
pubmed: 23092952
Gastroenterology. 2006 Jul;131(1):117-29
pubmed: 16831596
Cell Syst. 2019 Apr 24;8(4):329-337.e4
pubmed: 30954475
Inflamm Bowel Dis. 2022 Feb 1;28(2):299-308
pubmed: 34251431
Proc Natl Acad Sci U S A. 2016 Nov 29;113(48):13833-13838
pubmed: 27849619
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Gut. 2020 Nov;69(11):1939-1951
pubmed: 32111634
Int Immunopharmacol. 2022 Dec;113(Pt A):109310
pubmed: 36274484
Mucosal Immunol. 2014 May;7(3):579-88
pubmed: 24129163
Front Immunol. 2022 Oct 04;13:1020902
pubmed: 36275703
Front Immunol. 2018 Jun 07;9:1250
pubmed: 29930551
J Innate Immun. 2018;10(3):189-201
pubmed: 29393221
Nat Rev Immunol. 2008 Nov;8(11):829-35
pubmed: 18949018
Respir Med. 2011 Aug;105(8):1129-39
pubmed: 21367592
Arthritis Res Ther. 2018 Aug 9;20(1):173
pubmed: 30092845
J Biol Chem. 2021 Jul;297(1):100871
pubmed: 34126068
Cell Metab. 2020 Nov 3;32(5):889-900.e7
pubmed: 33147486
DNA Res. 2005;12(6):429-39
pubmed: 16769699
Cell Mol Gastroenterol Hepatol. 2016 Sep 20;3(1):72-81
pubmed: 28174758
Front Immunol. 2017 May 23;8:598
pubmed: 28588585
Nat Rev Gastroenterol Hepatol. 2022 Dec;19(12):785-803
pubmed: 36097076
Front Genet. 2021 Nov 04;12:782005
pubmed: 34804130
Mol Cell Biol. 2016 Jan 25;36(7):1124-35
pubmed: 26811327
Sci Rep. 2019 Aug 28;9(1):12479
pubmed: 31462669
Cell Mol Gastroenterol Hepatol. 2021;12(5):1809-1830
pubmed: 34237462
Nat Rev Immunol. 2014 Oct;14(10):667-85
pubmed: 25234148
Lupus. 2019 Nov;28(13):1524-1533
pubmed: 31660791
Nat Methods. 2017 Apr;14(4):417-419
pubmed: 28263959
J Exp Med. 2017 May 1;214(5):1547-1555
pubmed: 28420733
Front Immunol. 2021 Dec 03;12:799788
pubmed: 34925385
Front Immunol. 2022 Jul 25;13:929520
pubmed: 35958572
J Cyst Fibros. 2011 Jun;10 Suppl 2:S172-82
pubmed: 21658636
Cell Mol Gastroenterol Hepatol. 2021;12(1):229-250
pubmed: 33515804
Cell Stem Cell. 2013 Dec 5;13(6):653-8
pubmed: 24315439
Mol Metab. 2022 Sep;63:101546
pubmed: 35817394
Immunol Rev. 2014 Jul;260(1):8-20
pubmed: 24942678
mBio. 2014 Sep 30;5(5):e01548-14
pubmed: 25271284
J Transl Med. 2017 Apr 8;15(1):73
pubmed: 28388917