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

• Published in: Journal of neuroimmunology 2012-03, Vol.244 (1), p.35-44
• Main Authors: Cusick, Matthew F, Libbey, Jane E, Trede, Nikolaus S, Eckels, David D, Fujinami, Robert S
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; Compound; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Experimental autoimmune encephalomyelitis; Female; Human T cell; Humans; Hydrazones - therapeutic use; Lymphocyte Activation - drug effects; Mice; Multiple Sclerosis - drug therapy; Neurology; Quinolines - therapeutic use; Small Molecule Libraries; T-Lymphocytes - drug effects; Zebrafish
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2011.12.024

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.