p38α deficiency ameliorates psoriasis development by downregulating STAT3-mediated keratinocyte proliferation and cytokine production.

Psoriasis / metabolism STAT3 Transcription Factor / metabolism Keratinocytes / metabolism Animals Cell Proliferation Mice Mitogen-Activated Protein Kinase 14 / metabolism Cytokines / metabolism Down-Regulation Mice, Knockout Interleukin-17 / metabolism Mice, Inbred C57BL Disease Models, Animal Signal Transduction Humans Imiquimod

Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
15 Aug 2024
Historique:
received: 26 02 2024
accepted: 08 08 2024
medline: 16 8 2024
pubmed: 16 8 2024
entrez: 15 8 2024
Statut: epublish

Résumé

Psoriasis is characterized by keratinocyte (KC) hyperproliferation and inflammatory cell infiltration, but the mechanisms remain unclear. In an imiquimod-induced mouse psoriasiform model, p38 activity is significantly elevated in KCs and p38α specific deletion in KCs ameliorates skin inflammation. p38α signaling promotes KC proliferation and psoriasis-related proinflammatory gene expression during psoriasis development. Mechanistically, p38α enhances KC proliferation and production of inflammatory cytokines and chemokines by activating STAT3. While p38α signaling in KCs does not affect the expression of IL-23 and IL-17, it substantially amplifies the IL-23/IL-17 pathogenic axis in psoriasis. The therapeutic effect of IL-17 neutralization is associated with decreased p38 and STAT3 activities in KCs and targeting the p38α-STAT3 axis in KCs ameliorates the severity of psoriasis. As IL-17 also highly activates p38 and STAT3 in KCs, our findings reveal a sustained signaling circuit important for psoriasis development, highlighting p38α-STAT3 axis as an important target for psoriasis treatment.

Identifiants

DOI: 10.1038/s42003-024-06700-w PMID: 39147860
pubmed: 39147860
doi: 10.1038/s42003-024-06700-w
pii: 10.1038/s42003-024-06700-w
doi:

Substances chimiques

STAT3 Transcription Factor 0
Mitogen-Activated Protein Kinase 14 EC 2.7.11.24
Stat3 protein, mouse 0
Cytokines 0
Interleukin-17 0
Imiquimod P1QW714R7M

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

999

Subventions

Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 32341004, 82371758, 31670897
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82001702
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82200821
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 81971329

Informations de copyright

© 2024. The Author(s).

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Auteurs

Tingting Zheng (T)

Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China. ting616119@163.com.
ORCID: 0000-0001-9147-2115

Jiaqi Deng (J)

Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China.

Jiahong Wen (J)

Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China.

Shuxiu Xiao (S)

Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Haiyong Huang (H)

Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China.

Jiawen Shang (J)

Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China.

Luwen Zhang (L)

Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China.

Huan Chen (H)

Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China.

Jingyu Li (J)

Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China.

Yanyan Wang (Y)

Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China.

Suidong Ouyang (S)

Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China.

Meng Yang (M)

Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China.

Kinya Otsu (K)

Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
Cardiovascular Division, King's College London, London, UK.
ORCID: 0000-0001-9697-0711

Xinguang Liu (X)

Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Institute of Aging Research, Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Dongguan, China.

Gonghua Huang (G)

Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China. gonghua.huang@gdmu.edu.cn.
Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. gonghua.huang@gdmu.edu.cn.
ORCID: 0000-0003-1579-5478

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Classifications MeSH

Recherchemedicale.com › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Dermatoses papulosquameuses › Psoriasis › p38α deficiency ameliorates psoriasis...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription STAT › Facteur de transcription STAT-3 › p38α deficiency ameliorates psoriasis...
Recherchemedicale.com › Cellules › Cellules épithéliales › Kératinocytes › p38α deficiency ameliorates psoriasis...
Recherchemedicale.com › Eucaryotes › Animaux › p38α deficiency ameliorates psoriasis...
Recherchemedicale.com › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › p38α deficiency ameliorates psoriasis...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › p38α deficiency ameliorates psoriasis...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Mitogen-Activated Protein Kinases › p38 Mitogen-Activated Protein Kinases › Mitogen-Activated Protein Kinase 14 › p38α deficiency ameliorates psoriasis...
Recherchemedicale.com › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › p38α deficiency ameliorates psoriasis...
Recherchemedicale.com › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Régulation négative › p38α deficiency ameliorates psoriasis...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › p38α deficiency ameliorates psoriasis...
Recherchemedicale.com › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interleukines › Interleukine-17 › p38α deficiency ameliorates psoriasis...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › p38α deficiency ameliorates psoriasis...
Recherchemedicale.com › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › p38α deficiency ameliorates psoriasis...
Recherchemedicale.com › Phénomènes physiologiques cellulaires › Transduction du signal › p38α deficiency ameliorates psoriasis...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › p38α deficiency ameliorates psoriasis...
Recherchemedicale.com › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Quinoléines › Aminoquinoléines › Imiquimod › p38α deficiency ameliorates psoriasis...