Retinal astrocytes pretreated with NOD2 and TLR2 ligands activate uveitogenic T cells.
On entering the tissues, infiltrating autoreactive T cells must be reactivated locally to gain pathogenic activity. We have previously reported that, when activated by Toll-like receptor 3 (TLR3) and TLR4 ligands, retinal astrocytes (RACs) are able to function as antigen-presenting cells to re-activ...
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doaj-aa0189829d554e85985c48eeb01b540b2020-11-25T00:43:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0177e4051010.1371/journal.pone.0040510Retinal astrocytes pretreated with NOD2 and TLR2 ligands activate uveitogenic T cells.Guomin JiangDeming SunHenry J KaplanHui ShaoOn entering the tissues, infiltrating autoreactive T cells must be reactivated locally to gain pathogenic activity. We have previously reported that, when activated by Toll-like receptor 3 (TLR3) and TLR4 ligands, retinal astrocytes (RACs) are able to function as antigen-presenting cells to re-activate uveitogenic T cells and allow responder T cells to induce uveitis in mice. In the present study, we found that, although the triggering of TLR2 or nucleotide-binding oligomerization domain receptor 2 (NOD2) alone did not activate RACs, their combined triggering induced RACs with the phenotypes required to efficiently re-activate interphotoreceptor retinoid-binding protein (IRBP)-specific T cells. The synergistic effect of TLR2 and NOD2 ligands on RAC activation might be explained by the observations that bacterial lipoprotein (BLP, a TLR2 ligand) was able to upregulate NOD2 expression and the combination of BLP and muramyldipeptide (MDP, a NOD2 ligand) enhanced the expression of RICK (Rip2), the signaling molecule of NOD2. Moreover, the synergistic effect of MDP and BLP on RACs was lost when the RACs were derived from NOD2 knockout mice or were pre-treated with Rip2 antagonist. Thus, our data suggest that exogenous or endogenous molecules acting on both TLR2 and NOD2 on RACs might have an enhancing effect on susceptibility to autoimmune uveitis.http://europepmc.org/articles/PMC3393697?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Guomin Jiang Deming Sun Henry J Kaplan Hui Shao |
spellingShingle |
Guomin Jiang Deming Sun Henry J Kaplan Hui Shao Retinal astrocytes pretreated with NOD2 and TLR2 ligands activate uveitogenic T cells. PLoS ONE |
author_facet |
Guomin Jiang Deming Sun Henry J Kaplan Hui Shao |
author_sort |
Guomin Jiang |
title |
Retinal astrocytes pretreated with NOD2 and TLR2 ligands activate uveitogenic T cells. |
title_short |
Retinal astrocytes pretreated with NOD2 and TLR2 ligands activate uveitogenic T cells. |
title_full |
Retinal astrocytes pretreated with NOD2 and TLR2 ligands activate uveitogenic T cells. |
title_fullStr |
Retinal astrocytes pretreated with NOD2 and TLR2 ligands activate uveitogenic T cells. |
title_full_unstemmed |
Retinal astrocytes pretreated with NOD2 and TLR2 ligands activate uveitogenic T cells. |
title_sort |
retinal astrocytes pretreated with nod2 and tlr2 ligands activate uveitogenic t cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
On entering the tissues, infiltrating autoreactive T cells must be reactivated locally to gain pathogenic activity. We have previously reported that, when activated by Toll-like receptor 3 (TLR3) and TLR4 ligands, retinal astrocytes (RACs) are able to function as antigen-presenting cells to re-activate uveitogenic T cells and allow responder T cells to induce uveitis in mice. In the present study, we found that, although the triggering of TLR2 or nucleotide-binding oligomerization domain receptor 2 (NOD2) alone did not activate RACs, their combined triggering induced RACs with the phenotypes required to efficiently re-activate interphotoreceptor retinoid-binding protein (IRBP)-specific T cells. The synergistic effect of TLR2 and NOD2 ligands on RAC activation might be explained by the observations that bacterial lipoprotein (BLP, a TLR2 ligand) was able to upregulate NOD2 expression and the combination of BLP and muramyldipeptide (MDP, a NOD2 ligand) enhanced the expression of RICK (Rip2), the signaling molecule of NOD2. Moreover, the synergistic effect of MDP and BLP on RACs was lost when the RACs were derived from NOD2 knockout mice or were pre-treated with Rip2 antagonist. Thus, our data suggest that exogenous or endogenous molecules acting on both TLR2 and NOD2 on RACs might have an enhancing effect on susceptibility to autoimmune uveitis. |
url |
http://europepmc.org/articles/PMC3393697?pdf=render |
work_keys_str_mv |
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