Interleukin-33 Ameliorates Experimental Colitis through Promoting Th2/Foxp3+ Regulatory T-Cell Responses in Mice
Interleukin-33 Ameliorates Experimental Colitis through Promoting Th2/Foxp3+ Regulatory T-Cell Responses in Mice
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DOI：
10.2119/molmed.2011.00428
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发表时间：
2012-05-01
影响因子：
5.7
通讯作者：
Fang, Min
中科院分区：
文献类型：
--
作者：
Duan, Lihua;Chen, Jie;Fang, Min
克罗恩病(CD)以Th1、Th17细胞活化和调节性T细胞(Treg)缺乏为特征，导致肠道组织损伤和破坏。作为IL-1家族的一种新的细胞因子，IL-33在CD中的作用和机制尚不清楚。在这里，我们评估了IL-33对三硝基苯磺酸(TNBS)诱导的实验性结肠炎的影响和机制。我们发现，在TNBS治疗的小鼠中，IL-33的水平增加，而重组IL-33(rIL-33)的注射显著改善了TNBS介导的结肠组织损伤和结肠炎的临床症状。RIL-33的保护作用部分与显著增加Th2型细胞因子的诱导有关。重要的是，rIL-33治疗导致TNBS治疗的小鼠Foxp3表达显著上调，而Tregs的耗竭显著消除了IL-33在减少结肠炎发展方面的作用。值得注意的是，促进Treg发育的CD103(+)树突状细胞(DC：)水平也在rIL-33处理的小鼠肠系膜淋巴结和固有层中增加。RIL-33对CD103(+)DC诱导的影响是间接上调肠上皮细胞的结果，肠上皮细胞产生胸腺间质淋巴生成素和维甲酸，但不直接作用于DC。总之，我们的数据提供了明确的证据，表明IL-33在TNBS诱导的结肠炎中起到保护作用，这与Th1到Th2/Treg开关密切相关。因此，IL-33是开发CD新疗法的一个有前途的候选者。在线地址：http://www.molmed.org doi：10.2119/molmed.2011.00428
Crohn's disease (CD) is characterized by the activation of Th1 and Th17 cells and deficiency of regulatory T cells (Tregs), leading to intestine tissue injury and destruction. As a novel cytokine of the interleukin (IL)-1 family, the role and underlying mechanisms of IL-33 in CD remain poorly understood. Here, we assess the effects and mechanisms of IL-33 on the trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis that mimics human CD. We found that IL-33 levels were increased in the TNBS-treated mice, whereas recombinant IL-33 (rIL-33) administration substantially ameliorated TNBS-mediated colonic tissue injury and clinical symptoms of colitis. The protective effect of rIL-33 was partly associated with the markedly increased induction cf Th2-type cytokines. Importantly, rIL-33 treatment resulted in prominently upregulated Foxp3 expression in the TNBS-treated mice, and depletion of Tregs significantly abrogated the impact of IL-33 on reducing the development of colitis. Notably, the level of CD103(+) dendritic cells (DC:), which promotes development of Tregs, is also increased in mesenteric lymph node and lamina propria of rIL-33-treated mice. The impact of rIL-33 on CD103(+) DC induction was the result of indirectly upregulating intestine epithelial cells that produce thymic stromal lymphopoietin and retinoic acid but do not directly act on DCs. In conclusion, our data provide clear evidence that IL-33 plays a protective role in TNBS-induced colitis, which is closely related to a Th1-to-Th2/Treg switch. Thus, IL-33 is a promising candidate for the development of new treatments for CD. Online address: http://www.molmed.org doi: 10.2119/molmed.2011.00428