title: Human T cell expansion and experimental autoimmune encephalomyelitis inhibited by Lenaldekar, a small molecule discovered in a zebrafish screen.
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.
authors.affiliation: Department of Pathology, University of Utah, Salt Lake City, UT 84132, United States.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Cusick
authors.forename: Jane E
authors.initials: JE
authors.lastname: Libbey
authors.forename: Nikolaus S
authors.initials: NS
authors.lastname: Trede
authors.forename: David D
authors.initials: DD
authors.lastname: Eckels
authors.forename: Robert S
authors.initials: RS
authors.lastname: Fujinami
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D005260:Female; D006801:Humans; D006835:Hydrazones / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D009103:Multiple Sclerosis / Q000188:drug therapy*; D011804:Quinolines / Q000627:therapeutic use*; D054852:Small Molecule Libraries; D013601:T-Lymphocytes / Q000187:drug effects*; D015027:Zebrafish
chemical_list: C571887:1H-indole-3-carbaldehyde quinolin-8-yl-hydrazone; D006835:Hydrazones; D011804:Quinolines; D054852:Small Molecule Libraries