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

16 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 2012

Funding

We would like to thank Nikki J. Kennett, Braden T. McElreath and Daniel J. Doty for technical assistance, Susanne Ridges for thoughtful discussions and Kathleen Borick for the outstanding preparation of the manuscript. This work was supported by the Emma Mary Deland Foundation .

Keywords

  • Compound
  • Experimental autoimmune encephalomyelitis
  • Human T cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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