The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Macrophages and neutrophils are the targets for immune suppression by glucocorticoids in contact allergy
Open accessAbstract
Glucocorticoids (GCs) are widely used in the treatment of allergic skin conditions despite having numerous side effects. Here we use Cre/loxP-engineered tissue- and cell-specific and function-selective GC receptor (GR) mutant mice to identify responsive cell types and molecular mechanisms underlying the antiinflammatory activity of GCs in contact hypersensitivity (CHS). CHS was repressed by GCs only at the challenge phase, i.e., during reexposure to the hapten. Inactivation of the GR gene in keratinocytes or T cells of mutant mice did not attenuate the effects of GCs, but its ablation in macrophages and neutrophils abolished downregulation of the inflammatory response. Moreover, mice expressing a DNA binding-defective GR were also resistant to GC treatment. The persistent infiltration of macrophages and neutrophils in these mice is explained by an impaired repression of inflammatory cytokines and chemokines such as IL-1beta, monocyte chemoattractant protein-1, macrophage inflammatory protein-2, and IFN-gamma-inducible protein 10. In contrast TNF-alpha repression remained intact. Consequently, injection of recombinant proteins of these cytokines and chemokines partially reversed suppression of CHS by GCs. These studies provide evidence that in contact allergy, therapeutic action of corticosteroids is in macrophages and neutrophils and that dimerization GR is required.
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“This hypothesis is supported by prior work showing that repression of IL-1β, MIP-2, MCP-1, and IP-10 by GCs is hindered in macrophages isolated from GRdim mice (109, 110).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [110]
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Metadata
- Authors
- Tuckermann, J. P., Kleiman, A., Moriggl, R., Spanbroek, R., Neumann, A., Illing, A., Clausen, B. E., Stride, B., Förster, I., Habenicht, A. J. R., Reichardt, H. M., Tronche, F., Schmid, W., & Schütz, G.
- Affiliations
- German Cancer Research Center (DE)
- Ludwig Boltzmann Institute for Cancer Research (AT)
- Friedrich Schiller University Jena (DE)
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- Amsterdam UMC Location University of Amsterdam (NL)
- Heinrich Heine University Düsseldorf (DE)
- University of Göttingen (DE)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Tuckermann, Jan P.
- Schütz, Günther
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2007-05-01
- Volume
- 117
- Issue
- 5
- Pages
- 1381-1390
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1849982
- OpenAlex
- W2060990402
- Cited by
- 252
- References
- 54
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 9 · 2023: 13 · 2022: 12 · 2021: 16 · 2020: 17 · 2019: 17 · 2018: 18 · 2017: 16 · 2016: 15 · 2015: 11 · 2014: 14 · 2013: 11 · 2012: 20
- FWCI
- 13.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion)
- GRO (submittedVersion)
- Funders
- Deutsches Krebsforschungszentrum (69120, D-69120)
- Landsteiner Foundation for Blood Transfusion Research
- Deutsche Forschungsgemeinschaft (SFB405, SFB 636, SFB 488)
- Bundesministerium für Bildung und Forschung (01GS0477, 01GZ0310, KGCV1, 01GS0416)
- Austrian Science Fund (SFB‐F28)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (917.76.365)
- Leibniz-Gemeinschaft
- Topics
- Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- glucocorticoids, contact hypersensitivity, contact allergy, macrophages, neutrophils, glucocorticoid receptor, anti-inflammatory mechanism, chemokines, inflammatory cytokines, keratinocytes, T cells, skin inflammation
- MeSH terms
- Animals, Anti-Inflammatory Agents, Cells, Cultured, Dexamethasone, Immunosuppressive Agents, Macrophages, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Neutrophils, Receptors, Glucocorticoid, Drug Delivery Systems, Dermatitis, Allergic Contact, Mice
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