TGF-β limits IL-33 production and promotes the resolution of colitis through regulation of macrophage function.
TGF-β limits IL-33 production and promotes the resolution of colitis through regulation of macrophage function.
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DOI：
10.1002/eji.201041135
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发表时间：
2011-07
影响因子：
5.4
通讯作者：
Herbert, De'Broski R.
中科院分区：
文献类型：
--
作者：
Rani, Reena;Smulian, Alan G.;Greaves, David R.;Hogan, Simon P.;Herbert, De'Broski R.
巨噬细胞促进组织损伤或修复取决于它们的激活状态和局部细胞因子环境。目前尚不清楚转化生长因子β (TGF-β)的免疫抑制作用是否在体内巨噬细胞功能中起非冗余作用。我们在CD68启动子（CD68TGF-β dnrii）的控制下产生巨噬细胞特异性转基因小鼠，表达截断的TGF-β受体II，并将这些动物置于右旋糖酐-硫酸钠（DSS）结肠炎模型中。与转基因阴性小鼠相比，CD68TGF-βDNRII小鼠解决结肠炎的能力受损，表现为致病性增加、粒细胞炎症和杯状细胞再生延迟。CD68TGF-βDNRII小鼠产生的白细胞介素10明显减少，但IgE和IL-33+巨噬细胞水平高于对照组。这些数据与人类溃疡性结肠炎与IL-33产生增加之间的关联一致，并表明TGF-β可能通过直接影响巨噬细胞功能，至少部分地促进肠道炎症的抑制。
Macrophages promote tissue injury or repair depending upon on their activation status and the local cytokine milieu. It remains unclear whether the immunosuppressive effects of transforming growth factor beta (TGF-β) serve a non-redundant role in macrophage function in vivo. We generated macrophage-specific transgenic mice that express a truncated TGF-β receptor II under control of the CD68 promoter (CD68TGF-βDNRII)and subjected these animals to the dextran-sodium sulfate (DSS) model of colitis. CD68TGF-βDNRII mice have an impaired ability to resolve colitic inflammation as demonstrated by increased lethality, granulocytic inflammation, and delayed goblet cell regeneration compared to transgene negative littermates. CD68TGF-βDNRII mice produce significantly less interleukin 10, but have increased levels of IgE and IL-33+ macrophages than controls. These data are consistent with associations between ulcerative colitis and increased IL-33 production in humans and suggests that TGF-β may promote the suppression of intestinal inflammation, at least in part, through direct effects on macrophage function.
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影响因子：
15.8
作者：
Kang, Silvia S.;Bloom, Seth M.;Norian, Lyse A.;Geske, Michael J.;Flavell, Richard A.;Stappenbeck, Thaddeus S.;Allen, Paul M.
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影响因子：
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作者：
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DOI：
10.1152/ajpgi.00453.2007
发表时间：
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影响因子：
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作者：
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影响因子：
5.4
作者：
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通讯作者：
Weinstock, Joel V.