Interleukin-6 Derived from the Central Nervous System May Influence the Pathogenesis of Experimental Autoimmune Encephalomyelitis in a Cell-Dependent Manner.
Animals
CX3C Chemokine Receptor 1
/ metabolism
Central Nervous System
/ metabolism
Demyelinating Diseases
/ pathology
Encephalomyelitis, Autoimmune, Experimental
/ genetics
Female
Gene Expression Regulation
Glial Fibrillary Acidic Protein
/ metabolism
Gliosis
/ pathology
Inflammation
/ genetics
Interleukin-6
/ metabolism
Male
Mice, Inbred C57BL
Mice, Knockout
Myelin-Oligodendrocyte Glycoprotein
/ metabolism
Spinal Cord
/ pathology
MOG35-55peptide
conditional IL-6 knockout
experimental autoimmune encephalomyelitis
neuroinflammation
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
31 01 2020
31 01 2020
Historique:
received:
09
12
2019
revised:
27
01
2020
accepted:
28
01
2020
entrez:
7
2
2020
pubmed:
7
2
2020
medline:
11
2
2021
Statut:
epublish
Résumé
Interleukin-6 (IL-6) is a pleiotropic and multifunctional cytokine that plays a critical role in induction of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). Although EAE has always been considered a peripherally elicited disease, Il6 expression exclusively within central nervous system is sufficient to induce EAE development. Neurons, astrocytes, and microglia can secrete and respond to IL-6. To dissect the relevance of each cell source for establishing EAE, we generated and immunized conditional Il6 knockout mice for each of these cell types with myelin oligodendrocyte glycoprotein 35-55 (MOG The combined results reveal a minor role for Il6 expression in both astrocytes and microglia for symptomatology and neuropathology of EAE, whereas neuronal Il6 expression was not relevant for the variables analyzed.
Sections du résumé
BACKGROUND
Interleukin-6 (IL-6) is a pleiotropic and multifunctional cytokine that plays a critical role in induction of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). Although EAE has always been considered a peripherally elicited disease, Il6 expression exclusively within central nervous system is sufficient to induce EAE development. Neurons, astrocytes, and microglia can secrete and respond to IL-6.
METHODS
To dissect the relevance of each cell source for establishing EAE, we generated and immunized conditional Il6 knockout mice for each of these cell types with myelin oligodendrocyte glycoprotein 35-55 (MOG
RESULTS AND CONCLUSIONS
The combined results reveal a minor role for Il6 expression in both astrocytes and microglia for symptomatology and neuropathology of EAE, whereas neuronal Il6 expression was not relevant for the variables analyzed.
Identifiants
pubmed: 32023844
pii: cells9020330
doi: 10.3390/cells9020330
pmc: PMC7072597
pii:
doi:
Substances chimiques
CX3C Chemokine Receptor 1
0
Cx3cr1 protein, mouse
0
Glial Fibrillary Acidic Protein
0
Interleukin-6
0
Myelin-Oligodendrocyte Glycoprotein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
Références
Cytokine. 2014 Aug;68(2):86-93
pubmed: 24845797
Nat Immunol. 2007 Dec;8(12):1390-7
pubmed: 17994024
Genet Test Mol Biomarkers. 2014 Feb;18(2):127-30
pubmed: 24328460
Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10061-5
pubmed: 7694279
Mol Med. 1995 Nov;1(7):795-805
pubmed: 8612202
Int J Biol Sci. 2012;8(9):1254-66
pubmed: 23136554
Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13939-44
pubmed: 19666516
Int J Mol Sci. 2012 Oct 22;13(10):13667-79
pubmed: 23202972
Nat Neurosci. 2016 Jul 26;19(8):987-91
pubmed: 27459405
Lancet Neurol. 2019 Mar;18(3):269-285
pubmed: 30679040
J Immunol. 2009 Aug 1;183(3):2079-88
pubmed: 19597000
Glia. 2005 Aug 15;51(3):235-40
pubmed: 15812814
Nature. 2006 May 11;441(7090):235-8
pubmed: 16648838
Neurosci Lett. 2000 Nov 10;294(1):45-8
pubmed: 11044583
Brain. 2007 Nov;130(Pt 11):2800-15
pubmed: 17956913
Nat Immunol. 2017 Jan;18(1):74-85
pubmed: 27893700
Methods Mol Biol. 2018;1791:227-232
pubmed: 30006713
J Neuroimmunol. 2011 Jul;236(1-2):87-92
pubmed: 21621860
Glia. 2020 May;68(5):999-1016
pubmed: 31799746
J Neuroimmunol. 2001 Jun 1;116(2):168-77
pubmed: 11438171
Acta Neuropathol. 2017 Feb;133(2):223-244
pubmed: 27766432
J Immunol. 2010 May 1;184(9):4898-906
pubmed: 20351184
J Neuroinflammation. 2016 Jun 07;13(1):139
pubmed: 27266518
Immunity. 2013 Jan 24;38(1):79-91
pubmed: 23273845
Nat Immunol. 2005 Nov;6(11):1133-41
pubmed: 16200068
Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18460-5
pubmed: 19015529
Glia. 2002 Nov;40(2):140-55
pubmed: 12379902
J Neuroimmunol. 2018 May 15;318:1-7
pubmed: 29606295
Nat Med. 2005 Feb;11(2):146-52
pubmed: 15665833
Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):9041-6
pubmed: 18577591
Eur J Immunol. 1998 May;28(5):1727-37
pubmed: 9603480
Brain Behav Immun. 2013 Jan;27(1):162-73
pubmed: 23085146
Neuroendocrinology. 2019;109(2):113-130
pubmed: 30636247
Glia. 2013 Apr;61(4):587-600
pubmed: 23322593
Nat Med. 2007 Jan;13(1):89-94
pubmed: 17195839
Genes Dev. 2001 Apr 1;15(7):859-76
pubmed: 11297510
Brain Sci. 2016 May 17;6(2):
pubmed: 27196935
Eur J Immunol. 1998 Jul;28(7):2178-87
pubmed: 9692887
Int Immunol. 1998 May;10(5):703-8
pubmed: 9645618
J Immunol. 2006 Jul 1;177(1):566-73
pubmed: 16785554
Physiol Rev. 2011 Apr;91(2):461-553
pubmed: 21527731
Cell Mol Immunol. 2017 May 01;:
pubmed: 28458392
J Exp Med. 2013 Dec 16;210(13):2921-37
pubmed: 24323356
Ann Rheum Dis. 2007 Nov;66 Suppl 3:iii87-90
pubmed: 17934104
Neuroscientist. 2002 Jun;8(3):268-75
pubmed: 12061506
J Immunol. 2009 Mar 1;182(5):2628-40
pubmed: 19234157
Scand J Immunol. 1995 Jan;41(1):31-41
pubmed: 7824886
Immunity. 2010 Sep 24;33(3):424-36
pubmed: 20870176
Mol Cell Biol. 2002 Jul;22(14):5100-13
pubmed: 12077339
Ann Neurol. 2009 Dec;66(6):739-53
pubmed: 20035511
J Neurosci. 2009 Sep 16;29(37):11511-22
pubmed: 19759299
Acta Physiol (Oxf). 2014 Aug;211(4):585-96
pubmed: 24934978
J Neurol Sci. 1997 Feb 27;146(1):59-65
pubmed: 9077497
Mol Cell Biol. 1995 Sep;15(9):4971-9
pubmed: 7651415
Eur J Immunol. 1990 Jan;20(1):233-5
pubmed: 2307176
Nature. 2007 Jul 26;448(7152):484-487
pubmed: 17581588
Nat Protoc. 2006;1(4):1952-60
pubmed: 17487182
Med Sci Monit. 2001 Sep-Oct;7(5):914-8
pubmed: 11535934
Brain. 2003 May;126(Pt 5):1048-57
pubmed: 12690045
Trends Genet. 2018 May;34(5):333-340
pubmed: 29336844
J Neuroinflammation. 2015 Apr 22;12:79
pubmed: 25896970
Continuum (Minneap Minn). 2019 Jun;25(3):596-610
pubmed: 31162307
Brain Behav Immun. 2010 May;24(4):641-51
pubmed: 20138983