RAG2-/-, I kappa B-alpha-/- chimeras display a psoriasiform skin disease.
Nuclear factor-kappa B, a ubiquitous transcription factor involved in inflammatory and immune responses, is inappropriately activated in several immuno-related diseases, such as allograft rejection, or bronchial asthma. As nuclear factor-kappa B activity is regulated by inhibitor of kappa B (I kappa B), the gene encoding I kappa B-alpha was disrupted in mice to observe the in vivo effects of hyperactivation of nuclear factor-kappa B. I kappa B-alpha-/- mice have constitutive nuclear factor-kappa B activity, severe skin disease, and neonatal lethality. To determine the role of I kappa B-alpha deficient immunocytes in the pathogenesis of the skin disease in adult mice, we utilized the RAG2-deficient blastocyst complementation system to generate RAG2-/-, I kappa B-alpha-/- chimeras. These animals display a psoriasiform dermatitis characterized by hyperplastic epidermal keratinocytes and dermal infiltration of immunocytes, including lymphocytes. Skin grafts transferred from diseased chimeras to recipient nude mice produce hyperproliferative psoriasiform epidermal keratinocytes in response to stimulation. Furthermore, adoptive transfer of lymph node cells from diseased chimeras to RAG2-/- recipient mice recapitulates the disease. Taken together, these characterizations provide evidence to suggest that constitutive activation of nuclear factor-kappa B, due to deficiency in I kappa B-alpha, can invoke severe psoriasiform dermatitis in adult mice. J Invest Dermatol 115:1124-1133 2000
Chen
C L
CL
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2363, USA.
Yull
F E
FE
Cardwell
N
N
Singh
N
N
Strayhorn
W D
WD
Nanney
L B
LB
Kerr
L D
LD
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002678:Chimera; D016654:Genes, RAG-1; D020672:I-kappa B Proteins / Q000235:genetics*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D011565:Psoriasis / Q000235:genetics*; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000276:immunology
D020672:I-kappa B Proteins