Therapeutic efficacy of Tyro3, Axl, and Mer tyrosine kinase agonists in collagen-induced arthritis.
Therapeutic efficacy of Tyro3, Axl, and Mer tyrosine kinase agonists in collagen-induced arthritis.
复制标题
DOI：
10.1002/art.37786
复制
发表时间：
2013-03
影响因子：
--
通讯作者：
van de Loo, F. A. J.
中科院分区：
文献类型：
--
作者：
van den Brand, B. T.;Abdollahi-Roodsaz, S.;Vermeij, E. A.;Bennink, M. B.;Arntz, O. J.;Rothlin, C. V.;van den Berg, W. B.;van de Loo, F. A. J.
Toll样受体（TLR）对先天免疫的过度激活可导致自身炎症或自身免疫性疾病的发展。本研究评估TAM受体激活，TLR的生理负调节剂，通过其激动剂生长停滞特异性6（Gas 6）和蛋白S（Pros 1）来预防胶原诱导的关节炎。将过表达Gas 6和Prosl的腺病毒静脉内（i. v.）或关节内（i.a.）注射到小鼠体内。通过流式细胞术研究静脉注射小鼠的脾辅助性T细胞亚群，并通过i. v.和i.a.进行组织学评估。评估经i. a注射的小鼠的滑膜的细胞因子和细胞因子信号传导抑制因子（SOCS）表达。Pros 1显著降低踝关节肿胀时，全身过度表达。对膝关节的进一步分析显示，当Pros 1全身性过表达时，关节病理学中度减少，脾脏辅助性T细胞1显著减少。局部Gas 6过表达减少关节炎症和关节病理学。Pros 1处理显示出类似的保护趋势。一致地，Gas 6和Pros 1减少滑膜中的细胞因子产生。此外，Gas 6和Pros 1降低了IL-12和IL-23 mRNA水平，同时相应地降低了IFNγ和IL-17的产生。TAM配体过表达与SOCS 3的增加相关，这可能有助于关节炎的改善。我们提供了第一个证据，表明当全身或局部应用时，Gas 6和Pros 1对TAM受体的刺激可用于改善关节炎。TAM受体刺激限制了促炎信号传导和适应性免疫。这一途径为治疗类风湿性关节炎提供了一种新的策略。
Hyperactivation of innate immunity by Toll-Like Receptors (TLR) can contribute to the development of autoinflammatory or autoimmune diseases. This study evaluated TAM receptor activation, physiological negative regulators of TLRs, by their agonists Growth arrest specific 6 (Gas6) and Protein S (Pros1) to prevent collagen-induced arthritis. Adenoviruses overexpressing Gas6 and Pros1 were injected intravenously (i.v.) or intra-articularly (i.a.) into mice during collagen-induced arthritis. Splenic T-helper subsets of intravenously injected mice were studied by flow cytometry and knee joints of mice injected i.v. and i.a. were assessed histologically. Synovium of i.a injected mice was evaluated for cytokine and suppressor of cytokine signaling (SOCS) expression. Pros1 significantly reduced ankle joint swelling when overexpressed systemically. Further analysis of knee joints revealed a moderate reduction of joint pathology and a significant reduction of splenic T-helper 1 cells when Pros1 was overexpressed systemically. Local Gas6 overexpression decreased joint inflammation and joint pathology. Pros1 treatment showed a similar trend of protection. Consistently, Gas6 and Pros1 reduced cytokine production in synovium. Moreover, IL-12 and IL-23 mRNA levels were reduced by Gas6 and Pros1 with a corresponding decrease in IFNγ and IL-17 production. TAM ligand overexpression was associated with an increase in SOCS3, which likely contributed to the amelioration of arthritis We provide the first evidence that TAM receptor stimulation by Gas6 and Pros1 can be used to ameliorate arthritis when applied systemically or locally. TAM receptor stimulation limits proinflammatory signaling and the adaptive immunity. This pathway provides a novel strategy to combat rheumatoid arthritis.
登录
查看更多内容
影响因子：
--
作者：
Veenbergen, Sharon;Bennink, Miranda B.;van de Loo, Fons A. J.
通讯作者：
van de Loo, Fons A. J.
影响因子：
15.9
作者：
Abdollahi-Roodsaz, Shahla;Joosten, Leo A. B.;Van den Berg, Wim B.
通讯作者：
Van den Berg, Wim B.
影响因子：
4.4
作者：
Ehlting, Christian;Lai, Wi S.;Bode, Johannes G.
通讯作者：
Bode, Johannes G.
DOI：
10.4049/jimmunol.1101201
发表时间：
2011-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ye F;Han L;Lu Q;Dong W;Chen Z;Shao H;Kaplan HJ;Li Q;Lu Q
通讯作者：
Lu Q
MERTK是凋亡细胞诱导的T细胞耐受性所必需的。
影响因子：
15.3
作者：
Wallet, Mark A.;Sen, Pradip;Flores, Rafael R.;Wang, Yaming;Yi, Zuoan;Huang, Yingsu;Mathews, Clayton E.;Earp, H. Shelton;Matsushima, Glenn;Wang, Bo;Tisch, Roland
通讯作者：
Tisch, Roland