A stromal progenitor and ILC2 niche promotes muscle eosinophilia and fibrosis-associated gene expression.
Animals
Cell Proliferation
Chemokines, CC
/ genetics
Eosinophils
/ drug effects
Fibroblasts
/ drug effects
Fibrosis
Gene Expression
Gene Expression Profiling
Humans
Immunity, Innate
Interleukin-2
/ immunology
Interleukin-33
/ immunology
Interleukin-5
/ genetics
Intestines
/ drug effects
Lung
/ drug effects
Lymphocytes
/ drug effects
Mesenchymal Stem Cells
/ drug effects
Mice
Mice, Inbred mdx
Muscle, Skeletal
/ drug effects
Muscular Dystrophy, Duchenne
/ genetics
ILC2
ST2
chemokines
eosinophils
fibro/adipogenic progenitors
interleukin-33
interleukin-5
muscle inflammation
muscular dystrophy
type II innate immunity
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
13 04 2021
13 04 2021
Historique:
received:
16
06
2020
revised:
29
01
2021
accepted:
24
03
2021
entrez:
14
4
2021
pubmed:
15
4
2021
medline:
15
2
2022
Statut:
ppublish
Résumé
Despite the well-accepted view that chronic inflammation contributes to the pathogenesis of Duchenne muscular dystrophy (DMD), the function and regulation of eosinophils remain an unclear facet of type II innate immunity in dystrophic muscle. We report the observation that group 2 innate lymphoid cells (ILC2s) are present in skeletal muscle and are the principal regulators of muscle eosinophils during muscular dystrophy. Eosinophils were elevated in DMD patients and dystrophic mice along with interleukin (IL)-5, a major eosinophil survival factor that was predominantly expressed by muscle ILC2s. We also find that IL-33 was upregulated in dystrophic muscle and was predominantly produced by fibrogenic/adipogenic progenitors (FAPs). Exogenous IL-33 and IL-2 complex (IL-2c) expanded muscle ILC2s and eosinophils, decreased the cross-sectional area (CSA) of regenerating myofibers, and increased the expression of genes associated with muscle fibrosis. The deletion of ILC2s in dystrophic mice mitigated muscle eosinophilia and impaired the induction of IL-5 and fibrosis-associated genes. Our findings highlight a FAP/ILC2/eosinophil axis that promotes type II innate immunity, which influences the balance between regenerative and fibrotic responses during muscular dystrophy.
Identifiants
pubmed: 33852849
pii: S2211-1247(21)00311-9
doi: 10.1016/j.celrep.2021.108997
pmc: PMC8127948
mid: NIHMS1693709
pii:
doi:
Substances chimiques
Chemokines, CC
0
Il33 protein, mouse
0
Interleukin-2
0
Interleukin-33
0
Interleukin-5
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108997Subventions
Organisme : NCATS NIH HHS
ID : TL1 TR001069
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI060573
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL107202
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR062123
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD060848
Pays : United States
Organisme : NIAMS NIH HHS
ID : P50 AR070604
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR001416
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS120060
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001414
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI134657
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
Références
Front Physiol. 2019 Nov 29;10:1416
pubmed: 31849692
Front Immunol. 2017 Apr 28;8:510
pubmed: 28503177
JCI Insight. 2018 Nov 15;3(22):
pubmed: 30429376
Nat Immunol. 2011 Nov;12(11):1045-54
pubmed: 21946417
PLoS One. 2010 May 21;5(5):e10763
pubmed: 20505827
Skelet Muscle. 2014 Aug 25;4:7
pubmed: 25157321
Neuromuscul Disord. 2003 Mar;13(3):223-35
pubmed: 12609504
Ann Neurol. 2006 Jun;59(6):905-11
pubmed: 16607617
Nature. 1991 Aug 8;352(6335):536-9
pubmed: 1865908
Methods Mol Biol. 2018;1687:43-56
pubmed: 29067655
Nat Protoc. 2015 May;10(5):792-806
pubmed: 25927389
Nat Immunol. 2015 Feb;16(2):161-9
pubmed: 25531830
Nature. 2013 Oct 10;502(7470):245-8
pubmed: 24037376
Immunity. 2018 Jun 19;48(6):1220-1232.e5
pubmed: 29802020
Eur J Immunol. 2012 May;42(5):1106-16
pubmed: 22539286
Hum Mol Genet. 2008 Aug 1;17(15):2280-92
pubmed: 18430716
J Exp Med. 2013 Mar 11;210(3):535-49
pubmed: 23420878
Hum Mol Genet. 2009 Jul 15;18(14):2584-98
pubmed: 19401296
Immunity. 2012 Oct 19;37(4):649-59
pubmed: 23063330
J Neurol Sci. 2010 Jul 15;294(1-2):43-50
pubmed: 20471037
Hum Mol Genet. 2003 Aug 1;12(15):1813-21
pubmed: 12874102
Front Immunol. 2020 Jan 22;10:3114
pubmed: 32038635
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
J Immunol. 2008 Apr 1;180(7):4742-53
pubmed: 18354198
Neuromuscul Disord. 1994 May;4(3):183-91
pubmed: 7919967
Cell. 1987 Dec 24;51(6):919-28
pubmed: 3319190
Cell. 2013 Apr 11;153(2):376-88
pubmed: 23582327
Skelet Muscle. 2011 May 04;1(1):21
pubmed: 21798099
J Sports Med (Hindawi Publ Corp). 2020 Sep 1;2020:7059057
pubmed: 33376749
Annu Rev Immunol. 2003;21:425-56
pubmed: 12615888
Nat Rev Immunol. 2018 Jan;18(1):62-76
pubmed: 28853443
Am J Pathol. 2000 May;156(5):1789-96
pubmed: 10793090
J Immunol. 2019 Jul 15;203(2):476-484
pubmed: 31142604
Nature. 2010 Jan 28;463(7280):540-4
pubmed: 20023630
J Neurol Sci. 1995 Apr;129(2):97-105
pubmed: 7608742
Immunity. 2016 Feb 16;44(2):355-67
pubmed: 26872699
Nat Med. 2015 Jul;21(7):786-94
pubmed: 26053624
Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11489-94
pubmed: 20534524
Rare Dis. 2015 Feb 23;3(1):e1010966
pubmed: 26481612
Cell. 2013 Dec 5;155(6):1282-95
pubmed: 24315098
J Biochem. 1995 Nov;118(5):959-64
pubmed: 8749313