Loss of SOCS7 in mice results in severe cutaneous disease and increased mast cell activation
Loss of SOCS7 in mice results in severe cutaneous disease and increased mast cell activation
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DOI：
10.1016/j.clim.2009.04.003
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发表时间：
2009-08-01
影响因子：
8.6
通讯作者：
Brown, Jared M.
中科院分区：
文献类型：
--
作者：
Knisz, Judit;Banks, Alex;Brown, Jared M.
细胞因子信号转导抑制因子（SOCS）蛋白家族在细胞因子作用的负性调节中起核心作用，并与特应性疾病的发生发展有关。缺乏SOCS 7与小鼠的严重皮肤病有关。我们试图探索导致这种表型的潜在机制。分析皮肤样本并测量血清免疫球蛋白的产生。通过ELISA测定骨髓来源的肥大细胞的细胞因子产生。通过定量实时PCR评估肥大细胞胸腺基质淋巴细胞生成素（TSLP）的产生。获得的数据显示，与对照组相比，Socs 7（-/-）小鼠的血清IgE和IgG（1）产生增加，并表现出肥大细胞浸润增加，以及真皮中未经激发的肥大细胞脱粒。在体外，来自Socs 7（-/-）小鼠的骨髓来源的肥大细胞对IgE介导的刺激物过度活跃，促炎性细胞因子（IL-13、IL-6、TNF-α）的产生增加。此外，活化的Socs 7（-/-）骨髓来源的肥大细胞具有增加的IL-7 R α转录物，其是TSLP的异二聚体受体的一部分。最后，SOCS 7的缺乏伴随着Fc ε RI聚集后肥大细胞TSLP mRNA和蛋白质产生的增加。这些数据暗示SOCS 7参与过敏性炎症的调节，并证明SOCS 7参与肥大细胞中TSLP信号传导的调节。(C)2009年由Elsevier Inc.出版
The Suppressor of Cytokine Signaling (SOCS) protein family plays a central role in the negative regulation of cytokine action and has been implicated in the development of atopic diseases. Lack of SOCS7 is associated with severe skin disease in mice. We sought to explore the underlying mechanisms resulting in this phenotype. Skin samples were analyzed and serum immunoglobulin production was measured. Cytokine production by bone marrow derived mast cells was determined by ELISA. Mast cell thymic stromal lymphopoietin (TSLP) production was assessed by quantitative real-time PCR. Data obtained revealed that Socs7(-/-) mice have increased serum IgE and IgG(1) production and exhibit an increased mast cell infiltrate, as well as un-provoked mast cell degranulation in the dermis as compared to controls. In vitro, bone marrow derived mast cells from Socs7(-/-) mice are hyperactive to IgE-mediated stimuli, with elevated production of proinflammatory cytokines (IL-13, IL-6, TNF-alpha). Further, activated Socs7(-/-) bone marrow derived mast cells have increased IL-7R alpha transcript, which is part of the heterodimeric receptor for TSLP. Finally, lack of SOCS7 was accompanied by an increase in TSLP mRNA and protein production by mast cells following Fc epsilon RI aggregation. These data implicate SOCS7 in the modulation of allergic inflammation and demonstrate that SOCS7 is involved in the regulation of TSLP signaling in mast cells. (C) 2009 Published by Elsevier Inc.