Follistatin-like protein 1 promotes arthritis by up-regulating IFN-gamma.
Follistatin-like protein 1 promotes arthritis by up-regulating IFN-gamma.
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DOI：
10.4049/jimmunol.182.1.234
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发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Hirsch R
中科院分区：
文献类型：
--
作者：
Clutter SD;Wilson DC;Marinov AD;Hirsch R
卵泡listatin-like protein-1 （FSTL-1）是一种特征不明确的蛋白，在胶原诱导关节炎的早期阶段上调，通过基因转移可使关节炎恶化。目前的研究旨在确定FSTL-1促进关节炎的机制。将FSTL-1注射到小鼠脚掌，导致小鼠脚掌严重肿胀，并上调IFN-γ转录物和IFN-γ诱导的趋化因子CXCL10。缺乏T细胞的小鼠受到保护。IFN-γ的核心作用被证实，IFN-γ缺乏的小鼠在注射FSTL-1后没有表现出足跖肿胀。此外，暴露于弱TCR信号的小鼠脾脏细胞在FSTL-1存在下分泌IFN-γ增加了5倍。FSTL-1可由TLR4激动剂和致关节炎细胞因子IL-1β等先天免疫信号通过NFκB途径诱导。最后，FSTL-1在人类关节炎中被发现过表达，其中和抑制小鼠胶原诱导的关节炎，抑制关节炎关节中IFN-γ和CXCL10的产生。这些研究结果表明，FSTL-1通过增强IFN-γ信号通路在关节炎中起关键作用，并提示FSTL-1连接先天和适应性免疫反应的机制。
Follistatin-like protein-1 (FSTL-1) is a poorly characterized protein that is up-regulated in the early stage of collagen-induced arthritis and that exacerbates arthritis when delivered by gene transfer. The current study was designed to determine the mechanism by which FSTL-1 promotes arthritis. FSTL-1 was injected into mouse paws, resulting in severe paw swelling associated with up-regulation of IFN-γ transcript and the IFN-γ-induced chemokine, CXCL10. Mice depleted of T cells were protected. A central role for IFN-γ was confirmed by the finding that mice deficient in IFN-γ failed to exhibit paw swelling in response to injection of FSTL-1. Furthermore, IFN-γ secretion from mouse spleen cells exposed to a weak TCR signal was increased 5-fold in the presence of FSTL-1. FSTL-1 could be induced by innate immune signals, including TLR4 agonists and the arthritogenic cytokine, IL-1β, via an NFκB pathway. Finally, FSTL-1 was found to be overexpressed in human arthritis and its neutralization inhibited murine collagen-induced arthritis and suppressed IFN-γ and CXCL10 production in arthritic joints. These findings demonstrate that FSTL-1 plays a critical role in arthritis by enhancing IFN-γ signaling pathways and suggest a mechanism by which FSTL-1 bridges innate and adaptive immune responses.
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DOI：
10.1083/jcb.96.1.191
发表时间：
1983-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Sudo H;Kodama HA;Amagai Y;Yamamoto S;Kasai S
通讯作者：
Kasai S
影响因子：
4.4
作者：
Miyamae, Takako;Marinov, Anthony D.;Hirsch, Raphael
通讯作者：
Hirsch, Raphael
影响因子：
--
作者：
Kwak, Han Bok;Ha, Hyunil;Lee, Zang Hee
通讯作者：
Lee, Zang Hee
影响因子：
56.9
作者：
BROWN, K;GERSTBERGER, S;SIEBENLIST, U
通讯作者：
SIEBENLIST, U
影响因子：
4.4
作者：
Kim, EY;Teh, HS
通讯作者：
Teh, HS