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

doi:10.1016/j.jneuroim.2011.12.024

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

Surgery, Transplant Surgery Division

Research output: Contribution to journal › Article › peer-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 language	English (US)
Pages (from-to)	35-44
Number of pages	10
Journal	Journal of Neuroimmunology
Volume	244
Issue number	1-2
DOIs	https://doi.org/10.1016/j.jneuroim.2011.12.024
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jneuroim.2011.12.024

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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.",

keywords = "Compound, Experimental autoimmune encephalomyelitis, Human T cell",

author = "Cusick, {Matthew F.} and Libbey, {Jane E.} and Trede, {Nikolaus S.} and Eckels, {David D.} and Fujinami, {Robert S.}",

note = "Funding Information: 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 .",

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AU - Cusick, Matthew F.

AU - Libbey, Jane E.

AU - Trede, Nikolaus S.

AU - Eckels, David D.

AU - Fujinami, Robert S.

N1 - Funding Information: 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 .

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N2 - 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.

AB - 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.

KW - Compound

KW - Experimental autoimmune encephalomyelitis

KW - Human T cell

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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