High and low vitamin A therapies induce distinct FoxP3+ T-cell subsets and effectively control intestinal inflammation.
High and low vitamin A therapies induce distinct FoxP3+ T-cell subsets and effectively control intestinal inflammation.
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DOI：
10.1053/j.gastro.2009.06.063
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发表时间：
2009-10
期刊：
影响因子：
29.4
通讯作者：
Kim CH
中科院分区：
文献类型：
--
作者：
Kang SG;Wang C;Matsumoto S;Kim CH
视黄酸在诱导FoxP3+调节性T细胞中发挥积极作用。由于维甲酸是肠道中维生素a的代谢物，FoxP3+ T细胞调节肠道炎症，因此我们研究了维生素a状态对肠道中调节性T细胞和炎症的影响。SAMP1/YP模型是克罗恩病小鼠模型。我们制作维生素A缺乏、过量和正常SAMP1/YP小鼠，评估肠道炎症。我们还研究了不同维生素A含量诱导的FoxP3+ T细胞在SCID小鼠T细胞诱导的肠道炎症模型中的表型和功能。有限和过量的维生素A条件在体内诱导不同的FoxP3+ T细胞亚群，并改善SAMP1/YP小鼠的肠道炎症。维生素A含量有限的条件显著诱导CD103+CCR7+ FoxP3+细胞异常，而维生素A含量高的条件诱导CCR9+α4β7+ FoxP3+ T细胞异常。这两种FoxP3+ T细胞群，当转移到患有持续肠道炎症的小鼠体内时，在逆转炎症方面都非常有效。阻断或缺乏RARα的占用是在有限的维生素a可用性下诱导胸腺和外周高度抑制性CD103+CCR7+ FoxP3+细胞的机制。我们的研究结果发现了诱导高度抑制性FoxP3+调节性T细胞的新途径，可以有效地控制肠道炎症。该结果在治疗炎症性肠病方面具有重要意义。
Retinoic acid plays a positive role in induction of FoxP3+ regulatory T cells. Because retinoic acid is produced as a metabolite of vitamin A in the intestine and FoxP3+ T cells regulate intestinal inflammation, we investigated the impact of vitamin A status on the regulatory T cells and inflammation in the intestine. The SAMP1/YP model is a mouse model of Crohn’s disease. We made vitamin A deficient, excessive and normal SAMP1/YP mice and assessed the intestinal inflammation. We investigated also the phenotype and function of FoxP3+ T cells induced in different vitamin A availability in regulation of intestinal inflammation in a T cell-induced inflammation model in SCID mice. The limited and excessive vitamin A conditions induced distinct FoxP3+ T cell subsets in vivo and both ameliorated the intestinal inflammation in SAMP1/YP mice. The limited vitamin A condition greatly induced unusual CD103+CCR7+ FoxP3+ cells, while the high vitamin A condition induced CCR9+α4β7+ FoxP3+ T cells in the intestine. Both FoxP3+ T cell populations, when transferred into mice with ongoing intestinal inflammation, were highly effective in reversing the inflammation. Blockade or lack of occupancy of RARα is a mechanism to induce the highly suppressive CD103+CCR7+ FoxP3+ cells in both thymus and periphery in the limited vitamin A availability. Our results identify novel pathways of inducing highly suppressive FoxP3+ regulatory T cells that can effectively control intestinal inflammation. The results have significant ramifications in treating inflammatory bowel diseases.
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影响因子：
5.4
作者：
Huter, Eva N.;Punkosdy, George A.;Glass, Deborah D.;Cheng, Lily I.;Ward, Jerrold M.;Shevach, Ethan M.
通讯作者：
Shevach, Ethan M.
影响因子：
14.2
作者：
Bellinghausen, I;Klostermann, B;Saloga, J
通讯作者：
Saloga, J
DOI：
10.1073/pnas.192162899
发表时间：
2002-10-01
影响因子：
11.1
作者：
Lehmann, J;Huehn, J;Hamann, A
通讯作者：
Hamann, A
影响因子：
5.4
作者：
Schambach, Felix;Schupp, Michael;Reiner, Steven L.
通讯作者：
Reiner, Steven L.
影响因子：
32.4
作者：
Hill JA;Hall JA;Sun CM;Cai Q;Ghyselinck N;Chambon P;Belkaid Y;Mathis D;Benoist C
通讯作者：
Benoist C