The interrelated roles of TGF-β and IL-10 in the regulation of experimental colitis
The interrelated roles of TGF-β and IL-10 in the regulation of experimental colitis
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DOI：
10.4049/jimmunol.168.2.900
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发表时间：
2002-01-15
影响因子：
4.4
通讯作者：
Strober, W
中科院分区：
文献类型：
--
作者：
Fuss, IJ;Boirivant, M;Strober, W
在本研究中，我们明确了转化生长因子 -β（TGF -β）和白细胞介素 -10（IL -10）在调节2,4,6 - 三硝基苯磺酸（TNBS）结肠炎中发生的Th1介导的炎症反应中的关系。在初步研究中，我们发现给SJL/J小鼠喂食三硝基苯酚 - 半抗原化的结肠蛋白可诱导CD4(+)调节性T细胞，这些细胞能转移对TNBS结肠炎诱导的保护作用，并且这种保护作用与产生TGF -β的细胞相关，而非与产生IL -10的细胞相关。进一步的研究中，给SJL/J小鼠喂食半抗原化的结肠蛋白，然后在后续经直肠给予TNBS时分别给予抗 - TGF -β或抗 - IL -10，结果表明虽然两种抗体都消除了保护作用，但给予抗 - TGF -β可阻止TGF -β分泌，而IL -10分泌不受影响；然而给予抗 - IL -10则同时阻止了TGF -β和IL -10的分泌。因此，似乎IL -10的保护作用是其对TGF -β分泌影响的间接结果。为了进一步证实这一点，我们进行了过继转移研究，结果表明给予抗 - IL -10对供体小鼠中产生TGF -β的T细胞的诱导没有影响。然而，它确实抑制了这些细胞在受体小鼠中的后续扩增，可能是通过调节Th1 T细胞反应的强度来实现的，否则Th1 T细胞反应会抑制TGF -β反应。因此，这些研究表明TGF -β的产生是对Th1 T细胞介导的黏膜炎症进行反调节的主要机制，而IL -10作为促进TGF -β产生的次要因素是必需的。
In the present study, we define the relation between TGF-beta and IL-10 in the regulation of the Th1-mediated inflammation occurring in trinitrobenzene sulfonic acid (TNBS)-colitis. In initial studies, we showed that the feeding of trinitrophenol-haptenated colonic protein to SJL/J mice induces CD4(+) regulatory T cells that transfer protection from induction of TNBS-colitis, and that such protection correlates with cells producing TGF-beta, not IL-10. Further studies in which SJL/J mice were fed haptenated colonic protein, and then administered either anti-TGF-beta or anti-IL-10 at the time of subsequent TNBS administration per rectum, showed that while both Abs abolished protection, anti-TGF-beta administration prevented TGF-beta secretion, but left IL-10 secretion intact; whereas anti-IL-10 administration prevented both TGF-beta secretion and IL-10 secretion. Thus, it appeared that the protective effect of IL-10 was an indirect consequence of its effect on TGF-beta secretion. To establish this point further, we conducted adoptive transfer studies and showed that anti-IL-10 administration had no effect on induction of TGF-beta producing T cells in donor mice. However, it did inhibit their subsequent expansion in recipient mice, probably by regulating the magnitude of the Th1 T cell response which would otherwise inhibit the TGF-beta response. Therefore, these studies suggest that TGF-beta production is a primary mechanism of counter-regulation of Th1 T cell-mediated mucosal inflammation, and that IL-10 is necessary as a secondary factor that facilitates TGF-beta production.