Suppression of Autoimmune Retinal Inflammation by an Antiangiogenic Drug

Takeru Yoshimura; Ofra Benny; Lauren Bazinet; Robert J. D'Amato

doi:10.1371/journal.pone.0066219

Suppression of Autoimmune Retinal Inflammation by an Antiangiogenic Drug

Takeru Yoshimura, Ofra Benny^*, Lauren Bazinet, Robert J. D'Amato

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Chronic and recurrent uveitis account for approximately 10% of legal blindness in the western world. Autoimmune uveitis is driven by activated CD4⁺ T cells that differentiate into effector T helper cells (Th1, Th2, and Th17) which release proinflammatory cytokines that damage the retina. In this study we investigated the effect of the methionine aminopeptidase 2 (MetAP2) inhibitor, Lodamin, on T cell activation and differentiation. MetAp2 is an enzyme which regulates cellular protein synthesis and is highly expressed in T cells. Lodamin was found to suppress T cell receptor (TCR) mediated T cell proliferation and reduced the production of Th1 and Th17 cells. Further, Lodamin suppressed overall inflammation in the mouse model of experimental autoimmune uveitis (EAU) by a six fold. This effect was attributed in part to a reduction in retinal proinflammatory cytokines, down regulation of MetAP2 expression in purified lymph node CD4⁺ T cells, and a general normalization of the systemic immune reaction.

Original language	English
Article number	e66219
Journal	PLoS ONE
Volume	8
Issue number	6
DOIs	https://doi.org/10.1371/journal.pone.0066219
State	Published - 13 Jun 2013
Externally published	Yes

UN SDGs

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

Access to Document

10.1371/journal.pone.0066219

Cite this

@article{5bec750701db4f96b2f1f6a9c3b8c475,

title = "Suppression of Autoimmune Retinal Inflammation by an Antiangiogenic Drug",

abstract = "Chronic and recurrent uveitis account for approximately 10% of legal blindness in the western world. Autoimmune uveitis is driven by activated CD4+ T cells that differentiate into effector T helper cells (Th1, Th2, and Th17) which release proinflammatory cytokines that damage the retina. In this study we investigated the effect of the methionine aminopeptidase 2 (MetAP2) inhibitor, Lodamin, on T cell activation and differentiation. MetAp2 is an enzyme which regulates cellular protein synthesis and is highly expressed in T cells. Lodamin was found to suppress T cell receptor (TCR) mediated T cell proliferation and reduced the production of Th1 and Th17 cells. Further, Lodamin suppressed overall inflammation in the mouse model of experimental autoimmune uveitis (EAU) by a six fold. This effect was attributed in part to a reduction in retinal proinflammatory cytokines, down regulation of MetAP2 expression in purified lymph node CD4+ T cells, and a general normalization of the systemic immune reaction.",

author = "Takeru Yoshimura and Ofra Benny and Lauren Bazinet and D'Amato, {Robert J.}",

year = "2013",

month = jun,

day = "13",

doi = "10.1371/journal.pone.0066219",

language = "אנגלית",

volume = "8",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "6",

}

TY - JOUR

T1 - Suppression of Autoimmune Retinal Inflammation by an Antiangiogenic Drug

AU - Yoshimura, Takeru

AU - Benny, Ofra

AU - Bazinet, Lauren

AU - D'Amato, Robert J.

PY - 2013/6/13

Y1 - 2013/6/13

N2 - Chronic and recurrent uveitis account for approximately 10% of legal blindness in the western world. Autoimmune uveitis is driven by activated CD4+ T cells that differentiate into effector T helper cells (Th1, Th2, and Th17) which release proinflammatory cytokines that damage the retina. In this study we investigated the effect of the methionine aminopeptidase 2 (MetAP2) inhibitor, Lodamin, on T cell activation and differentiation. MetAp2 is an enzyme which regulates cellular protein synthesis and is highly expressed in T cells. Lodamin was found to suppress T cell receptor (TCR) mediated T cell proliferation and reduced the production of Th1 and Th17 cells. Further, Lodamin suppressed overall inflammation in the mouse model of experimental autoimmune uveitis (EAU) by a six fold. This effect was attributed in part to a reduction in retinal proinflammatory cytokines, down regulation of MetAP2 expression in purified lymph node CD4+ T cells, and a general normalization of the systemic immune reaction.

AB - Chronic and recurrent uveitis account for approximately 10% of legal blindness in the western world. Autoimmune uveitis is driven by activated CD4+ T cells that differentiate into effector T helper cells (Th1, Th2, and Th17) which release proinflammatory cytokines that damage the retina. In this study we investigated the effect of the methionine aminopeptidase 2 (MetAP2) inhibitor, Lodamin, on T cell activation and differentiation. MetAp2 is an enzyme which regulates cellular protein synthesis and is highly expressed in T cells. Lodamin was found to suppress T cell receptor (TCR) mediated T cell proliferation and reduced the production of Th1 and Th17 cells. Further, Lodamin suppressed overall inflammation in the mouse model of experimental autoimmune uveitis (EAU) by a six fold. This effect was attributed in part to a reduction in retinal proinflammatory cytokines, down regulation of MetAP2 expression in purified lymph node CD4+ T cells, and a general normalization of the systemic immune reaction.

UR - http://www.scopus.com/inward/record.url?scp=84878965911&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0066219

DO - 10.1371/journal.pone.0066219

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 23785488

AN - SCOPUS:84878965911

SN - 1932-6203

VL - 8

JO - PLoS ONE

JF - PLoS ONE

IS - 6

M1 - e66219

ER -

Suppression of Autoimmune Retinal Inflammation by an Antiangiogenic Drug

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this