PUBLICATION
Human T cell expansion and experimental autoimmune encephalomyelitis inhibited by Lenaldekar, a small molecule discovered in a zebrafish screen
- Authors
- Cusick, M.F., Libbey, J.E., Trede, N.S., Eckels, D.D., and Fujinami, R.S.
- ID
- ZDB-PUB-120117-21
- 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.
Citation
Cusick, M.F., Libbey, J.E., Trede, N.S., Eckels, D.D., and Fujinami, R.S. (2012) Human T cell expansion and experimental autoimmune encephalomyelitis inhibited by Lenaldekar, a small molecule discovered in a zebrafish screen. Journal of neuroimmunology. 244(1-2):35-44.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping