RORγt-Raftlin1 complex regulates the pathogenicity of Th17 cells and colonic inflammation.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
17 08 2023
17 08 2023
Historique:
received:
22
06
2022
accepted:
03
08
2023
medline:
21
8
2023
pubmed:
18
8
2023
entrez:
17
8
2023
Statut:
epublish
Résumé
Th17 cells that produce Interleukin IL-17 are pathogenic in many human diseases, including inflammatory bowel disease, but are, paradoxically, essential for maintaining the integrity of the intestinal barrier in a non-inflammatory state. However, the intracellular mechanisms that regulate distinct transcriptional profiles and functional diversity of Th17 cells remain unclear. Here we show Raftlin1, a lipid raft protein, specifically upregulates and forms a complex with RORγt in pathogenic Th17 cells. Disruption of the RORγt-Raftlin1 complex results in the reduction of pathogenic Th17 cells in response to Citrobacter rodentium; however, there is no effect on nonpathogenic Th17 cells in response to commensal segmented filamentous bacteria. Mechanistically, we show that Raftlin1 recruits distinct phospholipids to RORγt and promotes the pathogenicity of Th17 cells. Thus, we have identified a mechanism that drives the pathogenic function of Th17 cells, which could provide a platform for advanced therapeutic strategies to dampen Th17-mediated inflammatory diseases.
Identifiants
pubmed: 37591835
doi: 10.1038/s41467-023-40622-1
pii: 10.1038/s41467-023-40622-1
pmc: PMC10435467
doi:
Substances chimiques
Nuclear Receptor Subfamily 1, Group F, Member 3
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
4972Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK107733
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK130957
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG044271
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG013319
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI171226
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA266072
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI155786
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK115668
Pays : United States
Informations de copyright
© 2023. Springer Nature Limited.
Références
Nat Rev Immunol. 2017 Sep;17(9):535-544
pubmed: 28555673
J Immunol. 2004 Sep 1;173(5):2960-7
pubmed: 15322154
Immunity. 2009 Jan 16;30(1):92-107
pubmed: 19119024
Inflamm Bowel Dis. 2010 Oct;16(10):1808-13
pubmed: 20222127
J Immunol. 2016 May 1;196(9):3865-76
pubmed: 27022195
J Mol Biol. 2016 Feb 22;428(4):720-725
pubmed: 26410586
N Engl J Med. 2012 Mar 29;366(13):1190-9
pubmed: 22455413
Immunity. 2019 Jul 16;51(1):77-89.e6
pubmed: 31229354
J Biol Chem. 2001 May 11;276(19):16015-23
pubmed: 11279149
Sci Signal. 2015 Feb 24;8(365):ra22
pubmed: 25714464
Anal Chem. 2009 Jun 1;81(11):4356-68
pubmed: 19408941
Adv Biol Regul. 2017 Jan;63:6-14
pubmed: 27838257
Cytokine Growth Factor Rev. 2016 Aug;30:1-17
pubmed: 27481185
Immunity. 2009 Oct 16;31(4):677-89
pubmed: 19833089
J Immunol Methods. 2015 Jun;421:27-35
pubmed: 25769417
Cell. 2009 Aug 7;138(3):476-88
pubmed: 19646743
Methods Mol Biol. 2009;485:347-56
pubmed: 19020836
Cell. 2021 Aug 5;184(16):4154-4167.e12
pubmed: 34324837
BMB Rep. 2021 Apr;54(4):203-208
pubmed: 33172544
Cell Host Microbe. 2012 May 17;11(5):425-35
pubmed: 22607796
J Immunol. 2005 Sep 15;175(6):3800-9
pubmed: 16148126
J Immunol. 2009 May 15;182(10):5929-37
pubmed: 19414744
J Biol Chem. 2007 Mar 30;282(13):9358-9363
pubmed: 17277312
Nat Rev Microbiol. 2014 Sep;12(9):612-23
pubmed: 25088150
Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4615-22
pubmed: 20660719
Nat Commun. 2018 Oct 30;9(1):4515
pubmed: 30375383
Nat Protoc. 2016 Oct;11(10):1851-76
pubmed: 27606775
Cell Metab. 2015 Feb 03;21(2):286-298
pubmed: 25651181
Trends Biochem Sci. 2005 Feb;30(2):66-9
pubmed: 15691650
Inflamm Bowel Dis. 2015 Nov;21(11):2673-82
pubmed: 26313692
Rapid Commun Mass Spectrom. 2008 Jul;22(13):2115-24
pubmed: 18523984
Nature. 2021 Aug;596(7873):583-589
pubmed: 34265844
N Engl J Med. 2021 Jul 8;385(2):142-152
pubmed: 33891380
Mucosal Immunol. 2017 Sep;10(5):1108-1117
pubmed: 28612839
Circ Res. 2000 Sep 15;87(6):516-21
pubmed: 10988245
Proc Natl Acad Sci U S A. 2018 Jan 16;115(3):E458-E467
pubmed: 29282318
Immunity. 2008 Jan;28(1):29-39
pubmed: 18164222
Semin Immunol. 2013 Nov 30;25(5):342-51
pubmed: 24184014
Annu Rev Immunol. 2015;33:227-56
pubmed: 25581310
Trends Immunol. 2021 Nov;42(11):1037-1050
pubmed: 34635393
Protein Sci. 2018 Nov;27(11):1876-1892
pubmed: 30109749
Nat Med. 2013 Jul;19(7):824-5
pubmed: 23836225
EMBO J. 2003 Jun 16;22(12):3015-26
pubmed: 12805216
Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):12163-8
pubmed: 25092323
Mol Cell Biol. 2007 Oct;27(19):6669-85
pubmed: 17664281
Microbiol Immunol. 1995;39(8):555-62
pubmed: 7494493
Mol Cell Endocrinol. 2011 Mar 1;334(1-2):3-13
pubmed: 20615454
Methods Enzymol. 2014;536:87-94
pubmed: 24423269
Nat Immunol. 2019 Dec;20(12):1594-1602
pubmed: 31745337
Br J Pharmacol. 2011 Oct;164(4):1079-106
pubmed: 21371012
Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):7061-6
pubmed: 26038559
Immunity. 2010 Jun 25;32(6):815-27
pubmed: 20620945
Cell Rep. 2022 Sep 13;40(11):111345
pubmed: 36103814
Immunity. 2019 Apr 16;50(4):892-906
pubmed: 30995505
Nat Immunol. 2016 Aug;17(8):997-1004
pubmed: 27322655
Gut. 2012 Dec;61(12):1693-700
pubmed: 22595313
Cell Commun Signal. 2018 Apr 3;16(1):12
pubmed: 29615051
Nature. 2009 Mar 5;458(7234):78-82
pubmed: 19262671
Infect Immun. 1993 Jan;61(1):303-6
pubmed: 8418051
Immunity. 2016 Nov 15;45(5):1078-1092
pubmed: 27851911
Cell. 2009 Oct 30;139(3):485-98
pubmed: 19836068
Arthritis Rheumatol. 2014 Jul;66(7):1693-704
pubmed: 24623718