Human T cell expansion and experimental autoimmune encephalomyelitis inhibited by Lenaldekar, a small molecule discovered in a zebrafish screen

Matthew F. Cusick, Jane E. Libbey, Nikolaus S. Trede, David D. Eckels, Robert S. Fujinami*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Immune-mediated diseases [multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE)] are driven by proliferating, highly activated autoreactive T-cells that are unresponsive to in vivo immunoregulatory mechanisms. The compound Lenaldekar (LDK) was identified in a zebrafish screen by inhibiting T-cell expansion. By monitoring mitogen- and antigen-driven proliferation, we found that LDK inhibited human and murine T-cell expansion in a non-cytolytic manner. This suppressive activity directly correlated with the degree of activation/proliferation of the T-cells. In testing LDK in an EAE model of MS, exacerbations were suppressed in treated animals. Therefore, LDK represents a novel therapeutic approach to T-cell-mediated autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)35-44
Number of pages10
JournalJournal of Neuroimmunology
Volume244
Issue number1-2
DOIs
StatePublished - Mar 1 2012

Keywords

  • Compound
  • Experimental autoimmune encephalomyelitis
  • Human T cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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