Neutrophil-Derived Myeloperoxidase Facilitates Both the Induction and Elicitation Phases of Contact Hypersensitivity
Open accessAbstract
Background: Allergic contact dermatitis (ACD) is a common skin disorder affecting an estimated 15-20% of the general population. The mouse model of ACD is contact hypersensitivity (CHS), which consists of two phases: induction and elicitation. Although neutrophils are required for both CHS disease phases their mechanisms of action are poorly understood. Neutrophils release myeloperoxidase (MPO) that through oxidation of biomolecules leads to cellular damage. Objectives: This study investigated mechanisms whereby MPO contributes to CHS pathogenesis. Methods: CHS was induced in mice using oxazolone (OX) as the initiating hapten applied to the skin. After 7 days, CHS was elicited by application of OX to the ear and disease severity was measured by ear thickness and vascular permeability in the ear. The role of MPO in the two phases of CHS was determined utilizing MPO-deficient mice and a specific MPO inhibitor. Results: During the CHS induction phase MPO-deficiency lead to a reduction in IL-1β production in the skin and a subsequent reduction in migratory dendritic cells (DC) and effector T cells in the draining lymph node. During the elicitation phase, inhibition of MPO significantly reduced both ear swelling and vascular permeability. Conclusion: MPO plays dual roles in CHS pathogenesis. In the initiation phase MPO promotes IL-1β production in the skin and activation of migratory DC that promote effector T cell priming. In the elicitation phase MPO drives vascular permeability contributing to inflammation. These results indicate that MPO it could be a potential therapeutic target for the treatment of ACD in humans.
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The MPO system has been involved in various skin pathologies, either serving as a causative factor or biomarker in inflammation, contact hypersensitivity and irritation, psoriasis, UV-damage, photoaging, and carcinogenesis.
“beyond a role in cutaneous innate immunity, the MPO system has also been involved in various skin pathologies, either serving as a causative factor or biomarker in inflammation, contact hypersensitivity and irritation, psoriasis, UV-damage, photoaging, and carcinogenesis (51–59).”
From Hypochlorous Acid: From Innate Immune Factor and Environmental Toxicant to Chemopreventive Agent Targeting Solar UV-Induced Skin Cancer (2022) · cites this paper as [58]
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- Authors
- Strzepa, A., Gurski, C. J., Dittel, L. J., Szczepanik, M., Pritchard, K. A., & Dittel, B. N.
- Affiliations
- Medical College of Wisconsin (US)
- Jagiellonian University (PL)
- Corresponding author
- Dittel, Bonnie N.
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2021-01-25
- Volume
- 11
- Pages
- 608871-608871
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC7868335
- OpenAlex
- W3121891695
- Cited by
- 26
- References
- 58
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 6 · 2023: 7 · 2022: 4 · 2021: 2
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Homo Politicus (Academy of Humanities and Economics in Lodz) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- National Multiple Sclerosis Society
- Topics
- Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Keywords
- myeloperoxidase, contact hypersensitivity, allergic contact dermatitis, neutrophils, oxazolone, IL-1β, dendritic cell migration, vascular permeability, MPO inhibitors, skin inflammation
- MeSH terms
- Animals, Cell Movement, Dendritic Cells, Dermatitis, Contact, Haptens, Inflammation, Lymph Nodes, Mice, Inbred C57BL, Peroxidase, Neutrophils, Oxazolone, Skin, T-Lymphocytes, Dermatitis, Allergic Contact, Mice, Interleukin-1beta
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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