Neutrophils inhibit γδ T cell functions in the imiquimod-induced mouse model of psoriasis.

Mice Animals Imiquimod Neutrophils NADP Psoriasis / chemically induced Disease Models, Animal Eczema NADPH Oxidases / genetics Disease Progression
gamma delta (gammadelta) T cells immunoregulation inflammatory cyotokines neutrophils skin inflammation

Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2022
Historique:
received: 20 09 2022
accepted: 31 10 2022
entrez: 5 12 2022
pubmed: 6 12 2022
medline: 7 12 2022
Statut: epublish

Résumé

Psoriasis is a chronic skin disease associated with deregulated interplays between immune cells and keratinocytes. Neutrophil accumulation in the skin is a histological feature that characterizes psoriasis. However, the role of neutrophils in psoriasis onset and development remains poorly understood. In this study, we utilized the model of psoriasiform dermatitis, caused by the repeated topical application of an imiquimod containing cream, in neutrophil-depleted mice or in mice carrying impairment in neutrophil functions, including p47phox -/- mice (lacking a cytosolic subunit of the phagocyte nicotinamide adenine dinucleotide phosphate - NADPH - oxidase) and Sykfl/fl MRP8-cre+ mice (carrying the specific deletion of the Syk kinase in neutrophils only), to elucidate the specific contribution of neutrophils to psoriasis development. By analyzing disease development/progression in neutrophil-depleted mice, we now report that neutrophils act as negative modulators of disease propagation and exacerbation by inhibiting gammadelta T cell effector functions via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mediated reactive oxygen species (ROS) production. We also report that Syk functions as a crucial molecule in determining the outcome of neutrophil and γδ T cell interactions. Accordingly, we uncover that a selective impairment of Syk-dependent signaling in neutrophils is sufficient to reproduce the enhancement of skin inflammation and γδ T cell infiltration observed in neutrophil-depleted mice. Overall, our findings add new insights into the specific contribution of neutrophils to disease progression in the IMQ-induced mouse model of psoriasis, namely as negative regulatory cells.

Sections du résumé

Background
Psoriasis is a chronic skin disease associated with deregulated interplays between immune cells and keratinocytes. Neutrophil accumulation in the skin is a histological feature that characterizes psoriasis. However, the role of neutrophils in psoriasis onset and development remains poorly understood.
Methods
In this study, we utilized the model of psoriasiform dermatitis, caused by the repeated topical application of an imiquimod containing cream, in neutrophil-depleted mice or in mice carrying impairment in neutrophil functions, including p47phox -/- mice (lacking a cytosolic subunit of the phagocyte nicotinamide adenine dinucleotide phosphate - NADPH - oxidase) and Sykfl/fl MRP8-cre+ mice (carrying the specific deletion of the Syk kinase in neutrophils only), to elucidate the specific contribution of neutrophils to psoriasis development.
Results
By analyzing disease development/progression in neutrophil-depleted mice, we now report that neutrophils act as negative modulators of disease propagation and exacerbation by inhibiting gammadelta T cell effector functions via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mediated reactive oxygen species (ROS) production. We also report that Syk functions as a crucial molecule in determining the outcome of neutrophil and γδ T cell interactions. Accordingly, we uncover that a selective impairment of Syk-dependent signaling in neutrophils is sufficient to reproduce the enhancement of skin inflammation and γδ T cell infiltration observed in neutrophil-depleted mice.
Conclusions
Overall, our findings add new insights into the specific contribution of neutrophils to disease progression in the IMQ-induced mouse model of psoriasis, namely as negative regulatory cells.

Identifiants

DOI: 10.3389/fimmu.2022.1049079 PMID: 36466913 PMC: PMC9709482
pubmed: 36466913
doi: 10.3389/fimmu.2022.1049079
pmc: PMC9709482
doi:

Substances chimiques

Imiquimod P1QW714R7M
NADP 53-59-8
NADPH Oxidases EC 1.6.3.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1049079

Informations de copyright

Copyright © 2022 Costa, Bevilacqua, Caveggion, Gasperini, Zenaro, Pettinella, Donini, Dusi, Constantin, Lonardi, Vermi, De Sanctis, Ugel, Cestari, Abram, Lowell, Rodegher, Tagliaro, Girolomoni, Cassatella and Scapini.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Références

J Immunol. 2011 Oct 15;187(8):4319-30
pubmed: 21918195
Proc Natl Acad Sci U S A. 2013 Jun 25;110(26):10723-8
pubmed: 23754427
Methods Mol Biol. 2020;2087:243-260
pubmed: 31728997
J Exp Med. 2013 Oct 21;210(11):2171-80
pubmed: 24127491
Clin Dev Immunol. 2012;2012:252460
pubmed: 21808651
PLoS Biol. 2018 May 11;16(5):e2004990
pubmed: 29750788
Cell Mol Life Sci. 2014 Jun;71(12):2335-46
pubmed: 24162933
Clin Immunol. 2020 Jan;210:108294
pubmed: 31678366
Autoimmun Rev. 2015 Apr;14(4):286-92
pubmed: 25445403
Br J Dermatol. 2020 Apr;182(4):840-848
pubmed: 31225638
Br J Dermatol. 2002 May;146(5):824-31
pubmed: 12000379
Immunol Rev. 2016 Sep;273(1):48-60
pubmed: 27558327
Exp Dermatol. 2017 Apr;26(4):305-311
pubmed: 27194625
Clin Exp Immunol. 2011 Oct;166(1):26-33
pubmed: 21910722
Proc Natl Acad Sci U S A. 2011 Oct 11;108(41):E823-32
pubmed: 21911371
J Allergy Clin Immunol. 2021 Jun;147(6):2030-2042
pubmed: 33259837
Int Immunopharmacol. 2013 Nov;17(3):638-50
pubmed: 23994464
Scand J Immunol. 2014 Dec;80(6):381-9
pubmed: 25345993
Eur J Immunol. 2014 Mar;44(3):819-30
pubmed: 24271816
Immunity. 2011 Oct 28;35(4):596-610
pubmed: 21982596
J Invest Dermatol. 2017 Mar;137(3):546-549
pubmed: 27955901
Immunology. 2018 Feb;153(2):225-237
pubmed: 28888033
Int J Mol Sci. 2021 Oct 26;22(21):
pubmed: 34769005
Mucosal Immunol. 2017 Jul;10(4):1056-1068
pubmed: 28051086
J Invest Dermatol. 2014 Jul;134(7):1912-1921
pubmed: 24569709
J Clin Invest. 2012 Jun;122(6):2252-6
pubmed: 22546855
Nat Rev Immunol. 2017 Apr;17(4):248-261
pubmed: 28287106
J Clin Invest. 2012 Nov;122(11):3965-76
pubmed: 23064362
J Am Acad Dermatol. 2000 Aug;43(2 Pt 2):391-5
pubmed: 10901732
Curr Opin Rheumatol. 2015 Mar;27(2):127-33
pubmed: 25599143
J Allergy Clin Immunol. 2008 Dec;122(6):1097-103
pubmed: 18823651
Front Immunol. 2019 Oct 09;10:2376
pubmed: 31649677
Nat Commun. 2016 Dec 16;7:13581
pubmed: 27982014
J Invest Dermatol. 2000 May;114(5):976-83
pubmed: 10771480
J Exp Med. 1995 Sep 1;182(3):751-8
pubmed: 7650482
J Immunol. 2011 Sep 1;187(5):2783-93
pubmed: 21813772
Cancer Res. 2001 Jun 15;61(12):4756-60
pubmed: 11406548
Lancet. 2015 Sep 5;386(9997):983-94
pubmed: 26025581
Blood. 2014 Jul 31;124(5):710-9
pubmed: 24923297
Clin Rev Allergy Immunol. 2016 Jun;50(3):377-89
pubmed: 27025861
J Allergy Clin Immunol. 2020 Jun;145(6):1535-1544
pubmed: 32283205
Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):3163-3168
pubmed: 28270598
Cell Rep. 2016 Feb 2;14(4):708-722
pubmed: 26776523
J Immunol. 2011 Jul 1;187(1):490-500
pubmed: 21606249
J Allergy Clin Immunol. 2018 Apr;141(4):1320-1333.e11
pubmed: 28935206
J Leukoc Biol. 2015 Jul;98(1):99-106
pubmed: 25917460
Eur J Immunol. 2013 Dec;43(12):3138-46
pubmed: 24254490
Sci Rep. 2016 Apr 22;6:24880
pubmed: 27101808
Nature. 2008 Jan 10;451(7175):211-5
pubmed: 18185592
Br J Dermatol. 2017 Dec;177(6):e321-e322
pubmed: 28369663
Arch Dermatol Res. 2007 Oct;299(8):359-66
pubmed: 17680257
Blood. 2017 Mar 9;129(10):1343-1356
pubmed: 28053192
J Dermatol. 2020 Feb;47(2):104-113
pubmed: 31833093
Immunity. 2002 Apr;16(4):547-58
pubmed: 11970878
Front Immunol. 2021 Feb 25;12:621956
pubmed: 33717124
PLoS One. 2014 Mar 07;9(3):e91146
pubmed: 24608112
Nat Rev Immunol. 2011 Jul 25;11(8):519-31
pubmed: 21785456
J Clin Invest. 2012 Jan;122(1):327-36
pubmed: 22156198
J Immunol. 2014 May 1;192(9):4361-9
pubmed: 24663678
Int J Dermatol. 2012 Apr;51(4):389-95; quiz 395-8
pubmed: 22435425
Tumour Biol. 2012 Feb;33(1):121-9
pubmed: 22081309
J Leukoc Biol. 2017 Sep;102(3):791-803
pubmed: 28642279
Physiol Rev. 2019 Apr 1;99(2):1223-1248
pubmed: 30758246
Front Immunol. 2021 Dec 15;12:788940
pubmed: 34975883
Int J Dermatol. 1999 Nov;38(11):876-70
pubmed: 10583941
Immunity. 2017 Jan 17;46(1):15-28
pubmed: 28099862
Blood. 2009 Nov 26;114(23):4871-82
pubmed: 19797524
BMC Immunol. 2012 Dec 07;13:65
pubmed: 23216912
J Immunol. 2009 May 1;182(9):5836-45
pubmed: 19380832

Auteurs

Sara Costa (S)

Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy.

Dalila Bevilacqua (D)

Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy.

Elena Caveggion (E)

Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy.

Sara Gasperini (S)

Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy.

Elena Zenaro (E)

Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy.

Francesca Pettinella (F)

Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy.

Marta Donini (M)

Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy.

Stefano Dusi (S)

Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy.

Gabriela Constantin (G)

Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy.

Silvia Lonardi (S)

Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.

William Vermi (W)

Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.

Francesco De Sanctis (F)

Division of Immunology, University of Verona, Verona, Italy.

Stefano Ugel (S)

Division of Immunology, University of Verona, Verona, Italy.

Tiziana Cestari (T)

Division of Immunology, University of Verona, Verona, Italy.

Clare L Abram (CL)

Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, United States.

Clifford A Lowell (CA)

Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, United States.

Pamela Rodegher (P)

Department of Diagnostics and Public Health, Unit of Forensic Medicine, University of Verona, Verona, Italy.

Franco Tagliaro (F)

Department of Diagnostics and Public Health, Unit of Forensic Medicine, University of Verona, Verona, Italy.

Giampiero Girolomoni (G)

Division of Dermatology and Venereology, University of Verona, Verona, Italy.

Marco A Cassatella (MA)

Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy.

Patrizia Scapini (P)

Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy.

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Classifications MeSH

Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Neutrophils inhibit γδ T cell functions in the...
Recherchemedicale.com › Eucaryotes › Animaux › Neutrophils inhibit γδ T cell functions in the...
Recherchemedicale.com › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Quinoléines › Aminoquinoléines › Imiquimod › Neutrophils inhibit γδ T cell functions in the...
Recherchemedicale.com › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Granulocytes neutrophiles › Neutrophils inhibit γδ T cell functions in the...
Recherchemedicale.com › Acides nucléiques, nucléotides et nucléosides › Nucléotides › Ribonucléotides › Nucléotides adényliques › NADP › Neutrophils inhibit γδ T cell functions in the...
Recherchemedicale.com › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Dermatoses papulosquameuses › Psoriasis › Neutrophils inhibit γδ T cell functions in the...
Recherchemedicale.com › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Neutrophils inhibit γδ T cell functions in the...
Recherchemedicale.com › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Dermatoses eczémateuses › Eczéma › Neutrophils inhibit γδ T cell functions in the...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › NADPH oxidase › Neutrophils inhibit γδ T cell functions in the...
Recherchemedicale.com › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › Neutrophils inhibit γδ T cell functions in the...