1α,25-dihydroxycholecalciferol and cyclosporine suppress induction and promote resolution of psoriasis in human skin grafts transplanted on to SCID mice

Tomas Norman Dam, Sewon Kang, Brian J. Nickoloff, J. J. Voorhees

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Accumulating evidence has emphasized the importance of immunocompetent cells in determining the psoriatic phenotype. We have investigated the effect of 1α,25-dihydroxycholecalciferol, the naturally occurring active form of vitamin D3, cyclosporine A, and interleukin-10 on the phenotype of human psoriatic skin xenotransplants. First, psoriatic skin transplants were injected with either 1α,25-dihydroxycholecalciferol, cyclosporine A, or interleukin-10. Second, we determined the ability of autologous lymphocytes, activated in vitro using staphylococcal enterotoxin B and interleukin-2 and then exposed to either 1α,25-dihydroxycholecalciferol or cyclosporine A, to induce psoriatic lesions if they were injected into the dermis of uninvolved skin grafts. We found that injections into transplanted psoriatic plaques of either 1α,25-dihydroxycholecalciferol or cyclosporine A, but not interleukin-10, resulted in a consistent reduction in the clinical and histologic score of psoriasis with remission towards uninvolved psoriatic skin. Injection of activated immunocytes into symptomless psoriatic skin grafts, changed the grafts towards plaque-type psoriasis with silvery scale, parakeratosis, elongated rete pegs, acanthosis, and dermal angiogenic reaction. In contrast, if activated immunocytes were exposed to 1α,25- dihydroxycholecalciferol or cyclosporine A prior to injection, only minimal changes occurred. It was determined that neither staphylococcal enterotoxin B and interleukin-2 activation by itself, nor the drugs investigated, changed the CD4/CD8 ratio of activated (CD25+) cells. Our results are consistent with the hypothesis that psoriasis may be induced by activated T lymphocytes, and indicate that novel immunomodulatory drugs can serve to inhibit the pathogenetic ability of immunocytes in psoriasis.

Original languageEnglish (US)
Pages (from-to)1082-1089
Number of pages8
JournalJournal of Investigative Dermatology
Volume113
Issue number6
DOIs
StatePublished - 1999
Externally publishedYes

Keywords

  • Immune deviation
  • Interleukin-10
  • Superantigens
  • Vitamin D

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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