Interleukin-4 receptor signaling modulates neuronal network activity.
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
06 06 2022
06 06 2022
Historique:
received:
06
09
2021
revised:
13
12
2021
accepted:
29
04
2022
entrez:
19
5
2022
pubmed:
20
5
2022
medline:
24
5
2022
Statut:
ppublish
Résumé
Evidence is emerging that immune responses not only play a part in the central nervous system (CNS) in diseases but may also be relevant for healthy conditions. We discovered a major role for the interleukin-4 (IL-4)/IL-4 receptor alpha (IL-4Rα) signaling pathway in synaptic processes, as indicated by transcriptome analysis in IL-4Rα-deficient mice and human neurons with/without IL-4 treatment. Moreover, IL-4Rα is expressed presynaptically, and locally available IL-4 regulates synaptic transmission. We found reduced synaptic vesicle pools, altered postsynaptic currents, and a higher excitatory drive in cortical networks of IL-4Rα-deficient neurons. Acute effects of IL-4 treatment on postsynaptic currents in wild-type neurons were mediated via PKCγ signaling release and led to increased inhibitory activity supporting the findings in IL-4Rα-deficient neurons. In fact, the deficiency of IL-4Rα resulted in increased network activity in vivo, accompanied by altered exploration and anxiety-related learning behavior; general learning and memory was unchanged. In conclusion, neuronal IL-4Rα and its presynaptic prevalence appear relevant for maintaining homeostasis of CNS synaptic function.
Identifiants
pubmed: 35587822
pii: 213227
doi: 10.1084/jem.20211887
pmc: PMC9123307
pii:
doi:
Substances chimiques
Receptors, Interleukin-4
0
Interleukin-4
207137-56-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : German Research Foundation
ID : CRC 1080
Organisme : Germany Excellence Strategy
ID : EXC 2030-390661388
Organisme : Federal Ministry of Education and Research
ID : VIP + HaltMS-03VP07030
Organisme : Progressive MS Alliance
ID : PA-1604-08492
Informations de copyright
© 2022 Hanuscheck et al.
Références
Sci Rep. 2020 Nov 6;10(1):19241
pubmed: 33159098
Nat Biotechnol. 2022 Apr;40(4):555-565
pubmed: 34795433
Annu Rev Neurosci. 2017 Jul 25;40:557-579
pubmed: 28598717
Neuron. 2020 Apr 8;106(1):37-65.e5
pubmed: 32027825
Curr Opin Neurobiol. 2019 Aug;57:17-25
pubmed: 30690332
Neuron. 2014 Oct 22;84(2):416-31
pubmed: 25374362
Proc Natl Acad Sci U S A. 2004 May 25;101(21):8180-5
pubmed: 15141078
Neural Comput. 2004 Aug;16(8):1661-87
pubmed: 15228749
Nat Hum Behav. 2021 Oct;5(10):1282-1291
pubmed: 34400814
Nature. 2020 Jan;577(7789):249-253
pubmed: 31853066
Neuron. 2009 Mar 12;61(5):774-85
pubmed: 19285473
Exp Neurol. 2014 Aug;258:1-4
pubmed: 24814714
J Vis Exp. 2010 Nov 14;(45):
pubmed: 21113115
Sci Transl Med. 2018 Feb 28;10(430):
pubmed: 29491183
J Immunol. 2012 Nov 1;189(9):4213-9
pubmed: 23087426
Nucleic Acids Res. 2002 Jan 1;30(1):207-10
pubmed: 11752295
Nat Rev Neurosci. 2004 Mar;5(3):173-83
pubmed: 14976517
J Neurosci. 2007 Oct 3;27(40):10714-21
pubmed: 17913905
J Neural Eng. 2018 Aug;15(4):046014
pubmed: 29623905
Mol Ther. 2018 Sep 5;26(9):2107-2118
pubmed: 30017878
Mol Psychiatry. 2018 Aug;23(8):1699-1710
pubmed: 29743582
Nature. 2006 Apr 20;440(7087):1054-9
pubmed: 16547515
Stat Med. 2004 Jun 30;23(12):1901-19
pubmed: 15195323
Cell. 2010 Mar 19;140(6):918-34
pubmed: 20303880
Trends Neurosci. 2013 Jun;36(6):315-24
pubmed: 23478065
Brain. 2009 May;132(Pt 5):1247-58
pubmed: 19179377
Cytokine Growth Factor Rev. 2014 Aug;25(4):403-13
pubmed: 25153998
J Neurosci. 2013 Oct 30;33(44):17278-89
pubmed: 24174661
Genome Biol. 2014;15(12):550
pubmed: 25516281
J Neurosci. 2002 Nov 1;22(21):9278-86
pubmed: 12417653
J Neurol Sci. 2005 Jun 15;233(1-2):163-6
pubmed: 15949502
Comput Intell Neurosci. 2011;2011:156869
pubmed: 21253357
Immunity. 2004 May;20(5):623-35
pubmed: 15142530
Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19313-7
pubmed: 24218581
Nat Immunol. 2020 Nov;21(11):1421-1429
pubmed: 32929273
Nat Rev Neurosci. 2014 Feb;15(2):84-97
pubmed: 24399084
Nat Neurosci. 2018 Oct;21(10):1392-1403
pubmed: 30258239
Brain. 2013 Apr;136(Pt 4):1048-66
pubmed: 23518712
J Neurosci. 2018 Sep 26;38(39):8388-8406
pubmed: 30120207
Bioinformatics. 2018 Sep 1;34(17):i884-i890
pubmed: 30423086
J Neurosci. 2013 Mar 13;33(11):4625-33
pubmed: 23486937
Nat Neurosci. 2002 Jan;5(1):19-26
pubmed: 11753414
Nat Neurosci. 2006 Feb;9(2):268-75
pubmed: 16415867
Nature. 2016 Jul 21;535(7612):425-9
pubmed: 27409813
Neuron. 1998 Oct;21(4):885-93
pubmed: 9808473
Behav Brain Res. 2018 Jan 15;336:1-7
pubmed: 28843862
Glia. 2016 Dec;64(12):2079-2092
pubmed: 27470986
J Immunol. 2017 Apr 1;198(7):2681-2688
pubmed: 28202615
J Neurosci. 2014 Jun 25;34(26):8904-17
pubmed: 24966389
Brain Res. 2013 Jun 26;1518:9-25
pubmed: 23632380
Genesis. 2001 Sep;31(1):37-42
pubmed: 11668676
J Clin Invest. 2015 Jun;125(6):2547
pubmed: 25938785
Neuron. 2010 Nov 18;68(4):639-53
pubmed: 21092855
Brain Sci. 2021 Feb 25;11(3):
pubmed: 33668974
Front Neuroinform. 2018 Apr 04;12:14
pubmed: 29670519
Prog Neurobiol. 2010 Aug;91(4):313-48
pubmed: 20438797
Nat Biotechnol. 2015 Mar;33(3):290-5
pubmed: 25690850
Ann Neurol. 2009 Sep;66(3):310-22
pubmed: 19798635
Brain Commun. 2020 Jul 20;2(2):fcaa112
pubmed: 32954348
Bioarchitecture. 2013 Jul-Aug;3(4):113-8
pubmed: 24721730
Genes Dev. 2001 Apr 1;15(7):859-76
pubmed: 11297510
Brain Res. 2015 Aug 18;1617:18-27
pubmed: 25110235
Brain. 2020 Dec 5;143(11):3393-3407
pubmed: 33150359
Cell Mol Neurobiol. 2020 Nov;40(8):1327-1338
pubmed: 32172457
Annu Rev Neurosci. 2008;31:47-67
pubmed: 18284372
Nat Commun. 2020 Apr 29;11(1):2099
pubmed: 32350248
Neuron. 2015 Sep 23;87(6):1131-1142
pubmed: 26402599
Nature. 2015 Jul 16;523(7560):337-41
pubmed: 26030524
Neuron. 2005 Oct 6;48(1):77-90
pubmed: 16202710
Curr Opin Neurobiol. 2011 Apr;21(2):345-52
pubmed: 21349698
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10838-43
pubmed: 9380721
Neural Plast. 2018 May 14;2018:8430123
pubmed: 29861718
Nature. 1995 Jun 8;375(6531):488-93
pubmed: 7777057
Nature. 2018 Aug;560(7717):185-191
pubmed: 30046111
Cell. 2017 Sep 21;171(1):217-228.e13
pubmed: 28890086
Trends Neurosci. 2009 Jul;32(7):392-401
pubmed: 19524307
Sci Adv. 2019 May 29;5(5):eaav4111
pubmed: 31149632
Trends Immunol. 2016 Feb;37(2):154-165
pubmed: 26775912
J Exp Psychol Gen. 2013 May;142(2):573-603
pubmed: 22774788
J Exp Med. 2010 May 10;207(5):1067-80
pubmed: 20439540
Neuron. 2007 Nov 21;56(4):621-39
pubmed: 18031681
Nat Rev Immunol. 2021 Aug;21(8):526-541
pubmed: 33649606
Front Aging Neurosci. 2017 Sep 20;9:304
pubmed: 29081745
Nat Protoc. 2008;3(11):1718-28
pubmed: 18927557
Sci Rep. 2017 Mar 28;7:45101
pubmed: 28349920
Neuron. 2021 Nov 17;109(22):3609-3618.e9
pubmed: 34793707
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Cytometry A. 2010 Dec;77(12):1160-8
pubmed: 20687200
NPJ Parkinsons Dis. 2021 May 13;7(1):41
pubmed: 33986285
Bioinformatics. 2015 Feb 15;31(4):608-9
pubmed: 25677125
Cell Death Differ. 2015 Sep;22(9):1425-36
pubmed: 25678324
Cell. 2009 Sep 18;138(6):1222-35
pubmed: 19766573
Mol Cell Neurosci. 2006 Jan;31(1):149-60
pubmed: 16297637
Neuron. 1999 Jun;23(2):399-409
pubmed: 10399944
Gene Ther. 2008 Apr;15(7):504-15
pubmed: 18239607
Cell Stem Cell. 2013 Mar 7;12(3):354-67
pubmed: 23472874
J Neurosci. 2015 Aug 12;35(32):11281-91
pubmed: 26269636
Nat Rev Immunol. 2005 Aug;5(8):629-40
pubmed: 16034365
Elife. 2014 Feb 25;3:e01524
pubmed: 24569478