Resolution of psoriasis by a leukocyte-targeting bacterial protein in a humanized mouse model

Karin Stenderup, Cecilia Rosada, Thomas N. Dam, Erica Salerno, Benjamin A. Belinka, Scott C. Kachlany

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Psoriasis is a very common chronic skin disease, affecting 2-3% of the world's population or more than 125 million individuals worldwide. The characteristic lesion of psoriasis is due to rapid proliferation and shortened transition of keratinocytes through the epidermis. Proinflammatory white blood cells (WBCs) migrate into the psoriatic plaques, and the pathogenic cytokine environment causes the changes in keratinocyte proliferation and differentiation. Enhanced migration of WBCs is due to the upregulation and activation of adhesion molecules such as leukocyte function antigen-1 (LFA-1), which binds intercellular adhesion molecule-1 (ICAM-1) on endothelial cells. Targeting LFA-1 and preventing interaction with ICAM-1 has proven an effective strategy for treating psoriasis. We show here that a natural leukocyte-targeting bacterial protein (leukotoxin (LtxA)) that binds LFA-1 can inhibit proliferation of activated WBCs from psoriasis patients and demonstrates significant therapeutic efficacy in a psoriasis xenograft transplantation model. In ex vivo studies, LtxA preferentially targeted proinflammatory WBC subtypes, including activated CD25 T cells and CD14 CD16 monocytes. LFA-1 has been shown to have a significant role in the pathogenesis of numerous autoimmune and inflammatory diseases, and we propose that LtxA may be a highly effective agent for treating these diseases.

Original languageEnglish (US)
Pages (from-to)2033-2039
Number of pages7
JournalJournal of Investigative Dermatology
Volume131
Issue number10
DOIs
StatePublished - Oct 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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