Cited by 252Contact Dermatitis and AllergiesDermatology and Skin DiseasesEstrogen and related hormone effects

Macrophages and neutrophils are the targets for immune suppression by glucocorticoids in contact allergy

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Tuckermann, Jan P., Kleiman, Anna, Moriggl, Richard, Spanbroek, Rainer, Neumann, Anita, Illing, Anett, Clausen, Björn E., Stride, Brenda +6 more·2007·Journal of Clinical Investigation

Abstract

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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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
Venue
Journal of Clinical Investigation
Published
2007-05-01
Volume
117
Issue
5
Pages
1381-1390
ISSN
0021-9738 (ISSN-L)
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
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 › Genetics › 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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