Tissue inhibitor of metalloproteinase 1 is preferentially expressed in Th1 and Th17 T-helper cell subsets and is a direct STAT target gene.
CD4(+) T helper (Th) cells differentiate into distinct effector subsets that are critical for host defense, but are also implicated in the pathogenesis of autoimmune disorders. Thelper17 (Th17) cells in particular are emerging as important drivers of multiple diseases including psoriasis, spondyloar...
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doaj-4500c340d896431282bb6da13789825a2020-11-24T20:52:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5936710.1371/journal.pone.0059367Tissue inhibitor of metalloproteinase 1 is preferentially expressed in Th1 and Th17 T-helper cell subsets and is a direct STAT target gene.Adewole AdamsonKamran GhoreschiMatthew RittlerQian ChenHong-Wei SunGolnaz VahediYuka KannoWilliam G Stetler-StevensonJohn J O'SheaArian LaurenceCD4(+) T helper (Th) cells differentiate into distinct effector subsets that are critical for host defense, but are also implicated in the pathogenesis of autoimmune disorders. Thelper17 (Th17) cells in particular are emerging as important drivers of multiple diseases including psoriasis, spondyloarthropathy and multiple sclerosis. To gain insight into the function of Th17 cells, we performed transcriptional profiling in hopes of elucidating products not previously recognized as being functionally relevant in these T cells. Herein, we demonstrate that tissue inhibitor of metalloproteinase 1 (TIMP1), a secreted protein with pleiotropic effects on cellular growth, survival and integrity of the extracellular matrix, is preferentially produced by Th17 and Th1 cells. We further show that Th1 and Th17 cell TIMP1 regulation follows separate mechanisms with a requirement for STAT4 in the former and STAT3 in the latter. Finally, we demonstrate that when restricted to T cells, expression of TIMP1 promotes neuropathology in experimental allergic encephalomyelitis.http://europepmc.org/articles/PMC3608653?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Adewole Adamson Kamran Ghoreschi Matthew Rittler Qian Chen Hong-Wei Sun Golnaz Vahedi Yuka Kanno William G Stetler-Stevenson John J O'Shea Arian Laurence |
spellingShingle |
Adewole Adamson Kamran Ghoreschi Matthew Rittler Qian Chen Hong-Wei Sun Golnaz Vahedi Yuka Kanno William G Stetler-Stevenson John J O'Shea Arian Laurence Tissue inhibitor of metalloproteinase 1 is preferentially expressed in Th1 and Th17 T-helper cell subsets and is a direct STAT target gene. PLoS ONE |
author_facet |
Adewole Adamson Kamran Ghoreschi Matthew Rittler Qian Chen Hong-Wei Sun Golnaz Vahedi Yuka Kanno William G Stetler-Stevenson John J O'Shea Arian Laurence |
author_sort |
Adewole Adamson |
title |
Tissue inhibitor of metalloproteinase 1 is preferentially expressed in Th1 and Th17 T-helper cell subsets and is a direct STAT target gene. |
title_short |
Tissue inhibitor of metalloproteinase 1 is preferentially expressed in Th1 and Th17 T-helper cell subsets and is a direct STAT target gene. |
title_full |
Tissue inhibitor of metalloproteinase 1 is preferentially expressed in Th1 and Th17 T-helper cell subsets and is a direct STAT target gene. |
title_fullStr |
Tissue inhibitor of metalloproteinase 1 is preferentially expressed in Th1 and Th17 T-helper cell subsets and is a direct STAT target gene. |
title_full_unstemmed |
Tissue inhibitor of metalloproteinase 1 is preferentially expressed in Th1 and Th17 T-helper cell subsets and is a direct STAT target gene. |
title_sort |
tissue inhibitor of metalloproteinase 1 is preferentially expressed in th1 and th17 t-helper cell subsets and is a direct stat target gene. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
CD4(+) T helper (Th) cells differentiate into distinct effector subsets that are critical for host defense, but are also implicated in the pathogenesis of autoimmune disorders. Thelper17 (Th17) cells in particular are emerging as important drivers of multiple diseases including psoriasis, spondyloarthropathy and multiple sclerosis. To gain insight into the function of Th17 cells, we performed transcriptional profiling in hopes of elucidating products not previously recognized as being functionally relevant in these T cells. Herein, we demonstrate that tissue inhibitor of metalloproteinase 1 (TIMP1), a secreted protein with pleiotropic effects on cellular growth, survival and integrity of the extracellular matrix, is preferentially produced by Th17 and Th1 cells. We further show that Th1 and Th17 cell TIMP1 regulation follows separate mechanisms with a requirement for STAT4 in the former and STAT3 in the latter. Finally, we demonstrate that when restricted to T cells, expression of TIMP1 promotes neuropathology in experimental allergic encephalomyelitis. |
url |
http://europepmc.org/articles/PMC3608653?pdf=render |
work_keys_str_mv |
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