MicroRNA-155 Is Essential for the T Cell-Mediated Control of Helicobacter pylori Infection and for the Induction of Chronic Gastritis and Colitis
MicroRNA-155 Is Essential for the T Cell-Mediated Control of Helicobacter pylori Infection and for the Induction of Chronic Gastritis and Colitis
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DOI：
10.4049/jimmunol.1101772
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发表时间：
2011-10-01
影响因子：
4.4
通讯作者：
Mueller, Anne
中科院分区：
文献类型：
--
作者：
Oertli, Mathias;Engler, Daniela B.;Mueller, Anne
microRNA控制对感染因子、过敏原和自身抗原的免疫应答，并通过转录后抑制其靶基因发挥作用。在这篇文章中，我们阐述了microRNA-155（miR-155）在控制胃肠道幽门螺杆菌感染和幽门螺杆菌发展中的作用。幽门螺杆菌引起的慢性胃炎和相关的胃肿瘤前病变。我们发现miR-155在实验感染小鼠的胃粘膜中上调，并且miR-155（-/-）小鼠不能控制H。幽门螺杆菌感染是病原体特异性Th 1和Th 17应答受损的结果。miR-155（-/-）小鼠在H.与野生型（WT）对应物相比，幽门特异性疫苗接种。由于T细胞对H. pylori，miR-155（-/-）小鼠发展不太严重的感染诱导的免疫病理学，表现为慢性萎缩性胃炎、上皮增生和肠化生。来自通过CD 3/CD 28交联活化的miR-155（-/-）小鼠的T细胞比wt T细胞扩增更少并且产生更少的IFN-γ和IL-17。最后，我们在本文中使用过继转移表明，miR-155（-/-）小鼠的表型可能是由于T细胞内在缺陷。与wt T细胞相反，来自感染供体的miR-155（-/-）T细胞不控制H。幽门螺杆菌感染的T细胞缺陷的受体，不分化成Th 1或Th 17细胞，并不导致免疫病理学。此外，在过继转移模型中，初始miR-155（-/-）T细胞不能诱导慢性Th 17驱动的结肠炎。总之，miR-155表达是Th 17/Th 1分化所必需的，而Th 17/Th 1分化是对H.一方面是幽门螺杆菌感染，另一方面是感染相关的免疫病理学。免疫学杂志，2011，187：3578-3586。
MicroRNAs govern immune responses to infectious agents, allergens, and autoantigens and function by posttranscriptional repression of their target genes. In this paper, we have addressed the role of microRNA-155 (miR-155) in the control of Helicobacter pylori infection of the gastrointestinal tract and the development of H. pylori-induced chronic gastritis and associated gastric preneoplastic pathology. We show that miR-155 is upregulated in the gastric mucosa of experimentally infected mice and that miR-155(-/-) mice fail to control H. pylori infection as a result of impaired pathogen-specific Th1 and Th17 responses. miR-155(-/-) mice are also less well protected against challenge infection after H. pylori-specific vaccination than their wild-type (wt) counterparts. As a consequence of their impaired T cell responses to H. pylori, miR-155(-/-) mice develop less severe infection-induced immunopathology manifesting as chronic atrophic gastritis, epithelial hyperplasia, and intestinal metaplasia. T cells from miR-155(-/-) mice that are activated by CD3/CD28 cross-linking expand less and produce less IFN-gamma and IL-17 than wt T cells. Finally, we show in this paper using adoptive transfers that the phenotypes of miR-155(-/-) mice are likely due to T cell-intrinsic defects. In contrast to wt T cells, miR-155(-/-) T cells from infected donors do not control H. pylori infections in T cell-deficient recipients, do not differentiate into Th1 or Th17 cells, and do not cause immunopathology. In addition, naive miR-155(-/-) T cells fail to induce chronic Th17-driven colitis in an adoptive transfer model. In conclusion, miR-155 expression is required for the Th17/Th1 differentiation that underlies immunity to H. pylori infection on the one hand and infection-associated immunopathology on the other. The Journal of Immunology, 2011, 187: 3578-3586.