Mice lacking the transcription factor RelB develop T cell-dependent skin lesions similar to human atopic dermatitis.

Abstract

Mice with a targeted disruption of the Rel / NF-kappaB family member RelB develop a complex inflammatory phenotype and hematopoietic abnormalities. RelB-deficient (relB(- / -)) mice were clinically normal until 4 - 10 weeks after birth when thickening of the skin and hair loss developed. Histological and immunohistochemical evaluation of relB(- / -) skin lesions revealed hyperkeratosis and marked epidermal hyperplasia. Many CD4(+) T cells and eosinophils mixed with lesser numbers of CD8(+) T cells and neutrophils were present in the dermis. There was a moderate increase of MHC class II-positive dermal dendritic cells and dermal mast cells. Increased expression of Th2 cytokines correlated with increased mRNA levels of eotaxin and CCR3 in relB(- / -) skin. The dermatitis did not develop in the offspring of relB(- / -) mice crossed with transgenic mice that lack peripheral T cells, demonstrating that the skin lesions were T cell dependent. The dermatitis observed in RelB-deficient mice had many similarities with atopic dermatitis in human patients including infiltrating CD4(+) T cells and eosinophils in the skin, increased number of eosinophils in the blood and increased serum IgE. Thus, the relB(- / -) mouse should be a useful model to study the pathogenesis of this common allergic human disease.

• Authors: D Barton, H HogenEsch, F Weih
• Journal: European journal of immunology (Eur J Immunol) Vol. 30 Issue 8 Pg. 2323-32 (Aug 2000) ISSN: 0014-2980 [Print] Germany
• PMID: 10940923 (Publication Type: Journal Article)

Chemical References

• Chemokines
• Cytokines
• Histocompatibility Antigens Class II
• Proto-Oncogene Proteins
• RELB protein, human
• Relb protein, mouse
• Transcription Factors
• Transcription Factor RelB
• Keratins

Topics

• Animals
• Chemokines (biosynthesis)
• Cytokines (biosynthesis)
• Dermatitis, Atopic (etiology)
• Histocompatibility Antigens Class II (analysis)
• Humans
• Keratins (biosynthesis)
• Mast Cells (physiology)
• Mice
• Mice, Inbred C57BL
• Neutrophils (physiology)
• Proto-Oncogene Proteins (deficiency, physiology)
• Skin (pathology)
• T-Lymphocytes (physiology)
• Transcription Factor RelB
• Transcription Factors (deficiency, physiology)