IL-4 acts on skin derived dendritic cells to promote the Th2 response to cutaneous sensitization and the development of allergic skin inflammation.

Atopic dermatitis IL-4 Th2 polarization allergic skin inflammation cutaneous sensitization dendritic cells

Journal

The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002

Informations de publication

Date de publication:
10 Jul 2024
Historique:
received: 03 11 2023
revised: 06 06 2024
accepted: 24 06 2024
medline: 13 7 2024
pubmed: 13 7 2024
entrez: 12 7 2024
Statut: aheadofprint

Résumé

Atopic dermatitis is characterized by scratching and a Th2-dominated local and systemic response to cutaneously encountered antigens. Dendritic cells (DCs) capture antigens in the skin and rapidly migrate to draining lymph nodes (dLNs) where they drive the differentiation of antigen-specific naïve T cells. Determine whether non-T cell-derived IL-4 acts on skin-derived DCs to promote the Th2 response to cutaneously encountered antigen and allergic skin inflammation. DCs from dLNs of ovalbumin (OVA)-exposed skin were analyzed by flow cytometry and for their ability to polarize OVA-specific naïve CD4 Scratching upregulated IL4 expression in human skin. Similarly, tape stripping caused rapid basophil-dependent upregulation of cutaneous Il4 expression in mouse skin. In vitro treatment of DCs from skin dLNs with IL-4 promoted their capacity to drive Th2 differentiation. DCs from dLNs of OVA-sensitized skin of Il4 Mechanical skin injury causes basophil-dependent upregulation of cutaneous IL-4. IL-4 acts on skin DCs that capture antigen and migrate to dLNs to promote their capacity for Th2 polarization and drive allergic skin inflammation.

Sections du résumé

BACKGROUND BACKGROUND
Atopic dermatitis is characterized by scratching and a Th2-dominated local and systemic response to cutaneously encountered antigens. Dendritic cells (DCs) capture antigens in the skin and rapidly migrate to draining lymph nodes (dLNs) where they drive the differentiation of antigen-specific naïve T cells.
OBJECTIVE OBJECTIVE
Determine whether non-T cell-derived IL-4 acts on skin-derived DCs to promote the Th2 response to cutaneously encountered antigen and allergic skin inflammation.
METHODS METHODS
DCs from dLNs of ovalbumin (OVA)-exposed skin were analyzed by flow cytometry and for their ability to polarize OVA-specific naïve CD4
RESULTS RESULTS
Scratching upregulated IL4 expression in human skin. Similarly, tape stripping caused rapid basophil-dependent upregulation of cutaneous Il4 expression in mouse skin. In vitro treatment of DCs from skin dLNs with IL-4 promoted their capacity to drive Th2 differentiation. DCs from dLNs of OVA-sensitized skin of Il4
CONCLUSION CONCLUSIONS
Mechanical skin injury causes basophil-dependent upregulation of cutaneous IL-4. IL-4 acts on skin DCs that capture antigen and migrate to dLNs to promote their capacity for Th2 polarization and drive allergic skin inflammation.

Identifiants

DOI: 10.1016/j.jaci.2024.06.021 PMID: 38996877
pubmed: 38996877
pii: S0091-6749(24)00682-1
doi: 10.1016/j.jaci.2024.06.021
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Auteurs

Juan Manuel Leyva-Castillo (JM)

Division of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, USA. Electronic address: Manuel.LeyvaCastillo@childrens.harvard.edu.

Mrinmoy Das (M)

Division of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, USA.

Maria Strakosha (M)

Division of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, USA.

Alex McGurk (A)

Division of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, USA.

Emilie Artru (E)

Division of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, USA.

Christy Kam (C)

Division of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, USA.

Mohammed Alasharee (M)

Division of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, USA.

Duane R Wesemann (DR)

Department of Medicine, Division of Allergy and Clinical Immunology, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA and the Broad Institute and Ragon Institute, Cambridge, MA.

Michio Tomura (M)

Laboratory of Immunology, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan.

Hajime Karasuyama (H)

Inflammation, Infection and Immunity Laboratory, Advanced Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

Frank Brombacher (F)

International Center for Genetic Engineering and Biotechnology & University of Cape Town & South Africa Medical Research Council, South Africa.

Raif S Geha (RS)

Division of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, USA. Electronic address: raif.geha@childrens.harvard.edu.

Classifications MeSH