Tissue inhibitor of metalloproteinase 1 is preferentially expressed in Th1 and Th17 T-helper cell subsets and is a direct STAT target gene.
Tissue inhibitor of metalloproteinase 1 is preferentially expressed in Th1 and Th17 T-helper cell subsets and is a direct STAT target gene.
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DOI：
10.1371/journal.pone.0059367
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Laurence A
中科院分区：
文献类型：
--
作者：
Adamson A;Ghoreschi K;Rittler M;Chen Q;Sun HW;Vahedi G;Kanno Y;Stetler-Stevenson WG;O'Shea JJ;Laurence A
CD4+ T辅助细胞（Th）分化成不同的效应亚群，对宿主防御至关重要，但也与自身免疫性疾病的发病机制有关。特别是per17 （Th17）细胞正在成为多种疾病的重要驱动因素，包括牛皮癣、脊椎关节病和多发性硬化症。为了深入了解Th17细胞的功能，我们进行了转录谱分析，希望能够阐明以前未被认为与这些T细胞功能相关的产物。在此，我们证明了组织金属蛋白酶1抑制剂（TIMP1），一种对细胞生长、存活和细胞外基质完整性具有多效作用的分泌蛋白，优先由Th17和Th1细胞产生。我们进一步表明，Th1和Th17细胞TIMP1的调控遵循不同的机制，前者需要STAT4，后者需要STAT3。最后，我们证明当局限于T细胞时，TIMP1的表达促进实验性变应性脑脊髓炎的神经病理。
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.
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DOI：
10.1073/pnas.0600666103
发表时间：
2006-05-23
影响因子：
11.1
作者：
Chen, Zhi;Laurence, Arian;O'Shea, John J.
通讯作者：
O'Shea, John J.
影响因子：
15.9
作者：
Crocker, Matthew;Ashley, Sue;Papadopoulos, Marios C.
通讯作者：
Papadopoulos, Marios C.
影响因子：
--
作者：
Chen, Zhi;Tato, Cristina M.;O'Shea, John J.
通讯作者：
O'Shea, John J.
DOI：
10.1084/jem.20030896
发表时间：
2003-12-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Murphy CA;Langrish CL;Chen Y;Blumenschein W;McClanahan T;Kastelein RA;Sedgwick JD;Cua DJ
通讯作者：
Cua DJ
影响因子：
5
作者：
Cenit, M. C.;Alcina, A.;Urcelay, E.
通讯作者：
Urcelay, E.