The alarmin IL-33 promotes regulatory T-cell function in the intestine.
The alarmin IL-33 promotes regulatory T-cell function in the intestine.
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DOI：
10.1038/nature13577
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发表时间：
2014-09-25
期刊：
影响因子：
64.8
通讯作者：
Powrie, Fiona
中科院分区：
文献类型：
--
作者：
Schiering, Chris;Krausgruber, Thomas;Chomka, Agnieszka;Froehlich, Anja;Adelmann, Krista;Wohlfert, Elizabeth A.;Pott, Johanna;Griseri, Thibault;Bollrath, Julia;Hegazy, Ahmed N.;Harrison, Oliver J.;Owens, Benjamin M. J.;Loehning, Max;Belkaid, Yasmine;Fallon, Padraic G.;Powrie, Fiona
Foxp3 +调节性T细胞在肠道中大量存在，它们可防止对自身和环境刺激产生失调的炎症反应。现在人们认识到，调节性T细胞（Treg细胞）会获得组织特异性适应性，这有助于它们的生存和功能；然而，控制肠道中Treg细胞反应的关键宿主因素却鲜为人知。白细胞介素 - 1家族成员白细胞介素 - 33（IL - 33）在上皮细胞的屏障部位组成性表达，在组织损伤后它作为一种内源性危险信号或警报素发挥作用。近期对人类的研究表明，炎症性肠病（IBD）患者的炎症病变部位白细胞介素 - 33水平较高，这提示该细胞因子在IBD的发病机制中起作用。在肠道中，在急性结肠炎的小鼠模型中白细胞介素 - 33既有保护作用也有致病作用，但其对慢性炎症的作用仍不明确。在此我们表明，白细胞介素 - 33受体ST2优先在结肠调节性T细胞（cTreg细胞）上表达，它可促进调节性T细胞的功能以及对炎症环境的适应。白细胞介素 - 33向T细胞发出的信号以多种方式刺激调节性T细胞的反应。首先，它增强转化生长因子 - β1（TGF - β1）介导的调节性T细胞分化；其次，它为炎症组织中调节性T细胞的聚集和维持提供必要信号。引人注目的是，白细胞介素 - 23作为炎症性肠病发病机制中的一种关键促炎细胞因子，通过抑制白细胞介素 - 33的反应性来抑制调节性T细胞的反应。这些结果表明了一种此前未被认识到的组织损伤内源性介质与一种主要抗炎途径之间的联系，并提示白细胞介素 - 33和白细胞介素 - 23之间的平衡可能是肠道免疫反应的关键调控因素。
Foxp3+ regulatory T cells are abundant in the intestine where they prevent dysregulated inflammatory responses to self and environmental stimuli. It is now appreciated that Treg cells acquire tissue-specific adaptations that facilitate their survival and function; however, key host factors controlling the Treg response in the intestine are poorly understood. IL-1 family member IL-33 is constitutively expressed in epithelial cells at barrier sites where it functions as an endogenous danger signal or alarmin following tissue damage. Recent studies in humans have described high levels of IL-33 in inflamed lesions of inflammatory bowel disease (IBD) patients suggesting a role for this cytokine in the pathogenesis of IBD. In the intestine, both protective and pathologic roles for IL-33 have been described in murine models of acute colitis but its contribution to chronic inflammation remains ill defined. Here we show that the IL-33 receptor ST2 is preferentially expressed on colonic Treg (cTreg) cells, where it promotes Treg function and adaptation to the inflammatory environment. IL-33 signaling into T cells stimulates Treg responses in several ways. Firstly, it enhances transforming growth factor-β1 (TGF-β1) mediated differentiation of Treg cells and secondly, it provides a necessary signal for Treg accumulation and maintenance in inflamed tissues. Strikingly, IL-23, a key pro-inflammatory cytokine in the pathogenesis of IBD, restrained Treg responses through inhibition of IL-33 responsiveness. These results demonstrate a hitherto unrecognized link between an endogenous mediator of tissue damage and a major anti-inflammatory pathway, and suggest that the balance between IL-33 and IL-23 may be a key controller of intestinal immune responses.
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影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
DOI：
10.4049/jimmunol.1300379
发表时间：
2013-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Furusawa J;Moro K;Motomura Y;Okamoto K;Zhu J;Takayanagi H;Kubo M;Koyasu S
通讯作者：
Koyasu S
影响因子：
5.7
作者：
Duan, Lihua;Chen, Jie;Fang, Min
通讯作者：
Fang, Min
影响因子：
30.5
作者：
Burzyn D;Benoist C;Mathis D
通讯作者：
Mathis D