title: MicroRNA-155 is essential for the T cell-mediated control of Helicobacter pylori infection and for the induction of chronic Gastritis and Colitis.
abstract: 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.
authors: Institute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland.
authors: Mathias
authors: M
authors: Oertli
authors: Daniela B
authors: DB
authors: Engler
authors: Esther
authors: E
authors: Kohler
authors: Manuel
authors: M
authors: Koch
authors: Thomas F
authors: TF
authors: Meyer
authors: Anne
authors: A
authors: Müller
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D002908:Chronic Disease; D003092:Colitis / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000276:immunology / Q000382:microbiology; D005756:Gastritis / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D016481:Helicobacter Infections / Q000235:genetics* / Q000276:immunology; D016480:Helicobacter pylori / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse