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‐κB 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.