ZFIN ID: ZDB-PUB-120117-21
Human T cell expansion and experimental autoimmune encephalomyelitis inhibited by Lenaldekar, a small molecule discovered in a zebrafish screen
Cusick, M.F., Libbey, J.E., Trede, N.S., Eckels, D.D., and Fujinami, R.S.
Date: 2012
Source: Journal of neuroimmunology   244(1-2): 35-44 (Journal)
Registered Authors: Trede, Nick
Keywords: human T cell, experimental autoimmune encephalomyelitis, compound
MeSH Terms:
  • Animals
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental/drug therapy*
  • Female
  • Humans
  • Hydrazones/therapeutic use*
  • Lymphocyte Activation/drug effects*
  • Mice
  • Multiple Sclerosis/drug therapy*
  • Quinolines/therapeutic use*
  • Small Molecule Libraries
  • T-Lymphocytes/drug effects*
  • Zebrafish
PubMed: 22245285 Full text @ J. Neuroimmunol.
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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.
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