Counterregulation between thymic stromal lymphopoietin– and IL-23–driven immune axes shapes skin inflammation in mice with epidermal barrier defects
| Autor: | Jiagui Li, Nathalie Jonca, Marie-Christine Birling, Aurelie Eisenmann, Mei Li, Sarra Zaafouri, Guy Serre, Pierre Hener, Juan Manuel Leyva-Castillo |
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| Přispěvatelé: | Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Clinique de la Souris, Freiburg Institute for Advanced Studies [Freiburg, Germany], Albert-Ludwigs-Universität Freiburg, Institut d’Etudes Avancées de l’Université de Strasbourg (USIAS), Université de Strasbourg (UNISTRA), CARBILLET, Véronique, Institut d’Etudes Avancées de l’Université de Strasbourg - Institute for Advanced Study (USIAS) |
| Rok vydání: | 2016 |
| Předmět: |
Keratinocytes
MESH: Signal Transduction 0301 basic medicine MESH: Receptor PAR-2 / metabolism peeling skin syndrome type B Epidermal barrier Dermatitis Interleukin-23 MESH: Mice Knockout Corneodesmosin Mice MESH: Inflammation / metabolism T-Lymphocyte Subsets IL-23 [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases Interleukin 23 Immunology and Allergy MESH: Animals MESH: T-Lymphocyte Subsets / metabolism Protease-activated receptor 2 Mice Knockout MESH: Keratinocytes / metabolism atopic dermatitis MESH: Dermatitis / metabolism integumentary system MESH: Epidermis / pathology 3. Good health Peeling skin syndrome IL-1β MESH: T-Lymphocyte Subsets / immunology MESH: Dermatitis / immunology [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases Cytokines Intercellular Signaling Peptides and Proteins MESH: Receptor PAR-2 / genetics medicine.symptom Signal Transduction Filaggrin MESH: Glycoproteins / deficiency Thymic stromal lymphopoietin mouse model MESH: Interleukin-23 / metabolism MESH: Dermatitis / pathology Immunology MESH: Immunomodulation Inflammation Biology Immunomodulation 03 medical and health sciences Immune system thymic stromal lymphopoietin T(H)2 skin inflammation corneodesmosin medicine Animals Receptor PAR-2 MESH: Intercellular Signaling Peptides and Proteins MESH: Mice Glycoproteins MESH: Epidermis / immunology MESH: Cytokines / metabolism T(H)17 medicine.disease MESH: Cytokines / genetics MESH: Epidermis / metabolism Disease Models Animal 030104 developmental biology MESH: Biomarkers Epidermis MESH: Disease Models Animal Biomarkers |
| Zdroj: | Journal of Allergy and Clinical Immunology Journal of Allergy and Clinical Immunology, Elsevier, 2016, 138 (1), pp.150-161.e13. ⟨10.1016/j.jaci.2016.01.013⟩ Journal of Allergy and Clinical Immunology, 2016, 138 (1), pp.150-161.e13. ⟨10.1016/j.jaci.2016.01.013⟩ |
| ISSN: | 0091-6749 |
| DOI: | 10.1016/j.jaci.2016.01.013 |
| Popis: | International audience; Background: Epidermal barrier dysfunction has been recognized as a critical factor in the initiation and exacerbation of skin inflammation, particularly in patients with atopic dermatitis (AD) and AD-like congenital disorders, including peeling skin syndrome type B. However, inflammatory responses developed in barrier-defective skin, as well as the underlying mechanisms, remained incompletely understood. Objective: We aimed to decipher inflammatory axes and the cytokine network in mouse skin on breakdown of epidermal stratum corneum barrier. Methods: We generated Cdsn(iep-/-) mice with corneodesmosin ablation in keratinocytes selectively in an inducible manner. We characterized inflammatory responses and cytokine expression by using histology, immunohistochemistry, ELISA, and quantitative PCR. We combined mouse genetic tools, antibody-mediated neutralization, signal-blocking reagents, and topical antibiotic treatment to explore the inflammatory axes. Results: We show that on breakdown of the epidermal stratum corneum barrier, type 2 and type 17 inflammatory responses are developed simultaneously, driven by thymic stromal lymphopoietin (TSLP) and IL-23, respectively. Importantly, we reveal a counterregulation between these 2 inflammatory axes. Furthermore, we show that protease-activated receptor 2 signaling is involved in mediating the TSLP/type 2 axis, whereas skin bacteria are engaged in induction of the IL-23/type 17 axis. Moreover, we find that IL-1β is induced in skin of Cdsn(iep-/-) mice and that blockade of IL-1 signaling suppresses both TSLP and IL-23 expression and ameliorates skin inflammation. Conclusion: The inflammatory phenotype in barrier-defective skin is shaped by counterregulation between the TSLP/type 2 and IL-23/type 17 axes. Targeting IL-1 signaling could be a promising therapeutic option for controlling skin inflammation in patients with peeling skin syndrome type B and other diseases related to epidermal barrier dysfunction, including AD. |
| Databáze: | OpenAIRE |
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