MicroRNA-155 is essential for the T cell-mediated control of Helicobacter pylori infection and for the induction of chronic Gastritis and Colitis
In: Journal of immunology (Baltimore, Md. : 1950), Jg. 187 (2011-09-02), Heft 7
Online
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Zugriff:
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-γ 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.
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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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Autor/in / Beteiligte Person: | Koch, Manuel ; Oertli, Mathias ; Müller, Anne ; Meyer, Thomas F. ; Engler, Daniela B. ; Kohler, Esther ; University of Zurich |
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Zeitschrift: | Journal of immunology (Baltimore, Md. : 1950), Jg. 187 (2011-09-02), Heft 7 |
Veröffentlichung: | 2011 |
Medientyp: | unknown |
ISSN: | 1550-6606 (print) |
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