Mice lacking the transcription factor RelB develop T cell-dependent skin lesions similar to human atopic dermatitis.
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.
Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, Karlsruhe, Germany.
D
D
Barton
H
H
HogenEsch
F
F
Weih
D000818:Animals; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D003876:Dermatitis, Atopic / Q000209:etiology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007633:Keratins / Q000096:biosynthesis; D008407:Mast Cells / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000502:physiology*; D012867:Skin / Q000473:pathology*; D013601:T-Lymphocytes / Q000502:physiology*; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000172:deficiency / Q000502:physiology*
D018925:Chemokines; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D011518:Proto-Oncogene Proteins; C497593:RELB protein, human; C497594:Relb protein, mouse; D014157:Transcription Factors; D051841:Transcription Factor RelB; D007633:Keratins