Transfer RNA fragments replace microRNA regulators of the cholinergic poststroke immune blockade.
Aged
Animals
Case-Control Studies
Female
Humans
Inflammation
/ etiology
Ischemic Stroke
/ genetics
Lipopolysaccharide Receptors
/ metabolism
Lipopolysaccharides
/ pharmacology
Male
Mice
MicroRNAs
/ blood
Middle Aged
Monocytes
/ physiology
Non-Neuronal Cholinergic System
/ genetics
Prospective Studies
RAW 264.7 Cells
RNA, Transfer
/ blood
acetylcholine
immunology
ischemic stroke
microRNA
transfer RNA fragment
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
22 12 2020
22 12 2020
Historique:
pubmed:
9
12
2020
medline:
20
2
2021
entrez:
8
12
2020
Statut:
ppublish
Résumé
Stroke is a leading cause of death and disability. Recovery depends on a delicate balance between inflammatory responses and immune suppression, tipping the scale between brain protection and susceptibility to infection. Peripheral cholinergic blockade of immune reactions fine-tunes this immune response, but its molecular regulators are unknown. Here, we report a regulatory shift in small RNA types in patient blood sequenced 2 d after ischemic stroke, comprising massive decreases of microRNA levels and concomitant increases of transfer RNA fragments (tRFs) targeting cholinergic transcripts. Electrophoresis-based size-selection followed by qRT-PCR validated the top six up-regulated tRFs in a separate cohort of stroke patients, and independent datasets of small and long RNA sequencing pinpointed immune cell subsets pivotal to these responses, implicating CD14
Identifiants
pubmed: 33288717
pii: 2013542117
doi: 10.1073/pnas.2013542117
pmc: PMC7768686
doi:
Substances chimiques
CD14 protein, human
0
Lipopolysaccharide Receptors
0
Lipopolysaccharides
0
MicroRNAs
0
RNA, Transfer
9014-25-9
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
32606-32616Informations de copyright
Copyright © 2020 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
Références
Front Mol Neurosci. 2018 Apr 06;11:88
pubmed: 29681794
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
Int J Mol Sci. 2013 Jan 22;14(1):2072-84
pubmed: 23340648
Genome Biol. 2014;15(12):550
pubmed: 25516281
Lancet Neurol. 2008 Oct;7(10):915-26
pubmed: 18722812
Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1404-9
pubmed: 23297232
PLoS One. 2014 Jun 09;9(6):e99283
pubmed: 24911610
Nat Immunol. 2014 Jun;15(6):503-11
pubmed: 24840981
Nat Methods. 2016 Apr;13(4):366-70
pubmed: 26950747
Lancet Neurol. 2019 May;18(5):439-458
pubmed: 30871944
Bioinformatics. 2017 Sep 15;33(18):2941-2942
pubmed: 28541403
Cell. 2015 May 7;161(4):790-802
pubmed: 25957686
Sci Rep. 2017 Feb 21;7:41184
pubmed: 28220888
Stroke. 2015 Nov;46(11):3232-40
pubmed: 26451017
Cell Mol Neurobiol. 2015 Apr;35(3):433-447
pubmed: 25410304
Science. 2011 Oct 7;334(6052):98-101
pubmed: 21921156
RNA Biol. 2010 Sep-Oct;7(5):573-6
pubmed: 20818168
J Clin Invest. 2019 Apr 30;129(7):2946-2951
pubmed: 31039137
Nucleic Acids Res. 2017 Sep 19;45(16):9290-9301
pubmed: 28934507
Nat Rev Neurosci. 2005 Oct;6(10):775-86
pubmed: 16163382
Sci Rep. 2016 Feb 11;6:20850
pubmed: 26865164
BMC Biol. 2014 Oct 01;12:78
pubmed: 25270025
Stroke. 2007 Feb;38(2 Suppl):770-3
pubmed: 17261736
Science. 2020 Jan 31;367(6477):528-537
pubmed: 31831638
J Immunol. 2015 Nov 1;195(9):4446-55
pubmed: 26416280
Cell Rep. 2019 Oct 15;29(3):764-777.e5
pubmed: 31618642
Cell. 2009 Jul 23;138(2):215-9
pubmed: 19632169
J Cereb Blood Flow Metab. 2009 May;29(5):994-1002
pubmed: 19293821
J Biol Chem. 2005 Nov 18;280(46):38247-58
pubmed: 16169848
Nature. 2017 Dec 7;552(7683):57-62
pubmed: 29186115
Immunity. 2009 Dec 18;31(6):965-73
pubmed: 20005135
Cancer Res. 2017 Jun 15;77(12):3194-3206
pubmed: 28446464
Cell Rep. 2018 Dec 18;25(12):3356-3370.e4
pubmed: 30566862
Cell Rep. 2018 Oct 30;25(5):1346-1358
pubmed: 30380423
Nat Med. 2017 Jun;23(6):723-732
pubmed: 28394332
Front Aging Neurosci. 2016 Feb 22;8:29
pubmed: 26941641
BMC Genomics. 2014 Jun 14;15:474
pubmed: 24928098
Neurology. 2011 Oct 4;77(14):1338-45
pubmed: 21940613
Mol Med. 2010 Jul-Aug;16(7-8):278-86
pubmed: 20464061
BMC Bioinformatics. 2009 Oct 12;10:328
pubmed: 19821977
Trends Immunol. 2018 Feb;39(2):123-134
pubmed: 29236673
Cell. 1994 Mar 11;76(5):821-8
pubmed: 7510216
Front Immunol. 2018 May 22;9:1108
pubmed: 29872438
Mol Med. 2016 Sep;22:156-161
pubmed: 27257683
Front Immunol. 2017 Sep 06;8:1085
pubmed: 28932225
J Cereb Blood Flow Metab. 2020 Apr;40(4):775-786
pubmed: 30966854
Proc Natl Acad Sci U S A. 2019 Apr 23;116(17):8451-8456
pubmed: 30962382
Brain. 2019 Apr 1;142(4):978-991
pubmed: 30860258
Front Immunol. 2018 Nov 05;9:2522
pubmed: 30455690
J Neurosci. 2016 Apr 13;36(15):4182-95
pubmed: 27076418
J Cereb Blood Flow Metab. 2017 Dec;37(12):3671-3682
pubmed: 27733675
Trends Neurosci. 2015 Jul;38(7):448-58
pubmed: 26100140
Eur Neurol. 2007;58(4):224-7
pubmed: 17823536
Nat Methods. 2017 Apr;14(4):417-419
pubmed: 28263959
J Cell Biol. 2009 Apr 6;185(1):35-42
pubmed: 19332886
EMBO J. 2007 Sep 19;26(18):4138-48
pubmed: 17762869
Bio Protoc. 2014 Jul 20;4(14):
pubmed: 27570796
Nature. 2000 May 25;405(6785):458-62
pubmed: 10839541
Elife. 2015 Aug 12;4:
pubmed: 26267216