RAG2-/-, IκB-α-/- chimeras display a psoriasiform skin disease

Chih Li Chen, Fiona E. Yull, Nancy Cardwell, Nagendra Singh, William David Strayhorn, Lillian B. Nanney, Lawrence D. Kerr

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Nuclear factor-κB, 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-κB activity is regulated by inhibitor of κB (IκB), the gene encoding IκB-α was disrupted in mice to observe the in vivo effects of hyperactivation of nuclear factor-κB. IκB-α-/- mice have constitutive nuclear factor-κB activity, severe skin disease, and neonatal lethality. To determine the role of IκB-α deficient immunocytes in the pathogenesis of the skin disease in adult mice, we utilized the RAG2-deficient blastocyst complementation system to generate RAG2-/-, IκB-α-/- 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-κB, due to deficiency in IκB-α, can invoke severe psoriasiform dermatitis in adult mice.

Original languageEnglish (US)
Pages (from-to)1124-1133
Number of pages10
JournalJournal of Investigative Dermatology
Volume115
Issue number6
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Keywords

  • IκB-α
  • Keratinocytes
  • Lymphocytes
  • Psoriasis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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  • Cite this

    Chen, C. L., Yull, F. E., Cardwell, N., Singh, N., Strayhorn, W. D., Nanney, L. B., & Kerr, L. D. (2000). RAG2-/-, IκB-α-/- chimeras display a psoriasiform skin disease. Journal of Investigative Dermatology, 115(6), 1124-1133. https://doi.org/10.1046/j.1523-1747.2000.00162.x