title: Micro-RNA-155-mediated control of heme oxygenase 1 (HO-1) is required for restoring adaptively tolerant CD4+ T-cell function in rodents.
abstract: T cells chronically stimulated by a persistent antigen often become dysfunctional and lose effector functions and proliferative capacity. To identify the importance of micro-RNA-155 (miR-155) in this phenomenon, we analyzed mouse miR-155-deficient CD4(+) T cells in a model where the chronic exposure to a systemic antigen led to T-cell functional unresponsiveness. We found that miR-155 was required for restoring function of T cells after programmed death receptor 1 blockade. Heme oxygenase 1 (HO-1) was identified as a specific target of miR-155 and inhibition of HO-1 activity restored the expansion and tissue migration capacity of miR-155(-/-) CD4(+) T cells. Moreover, miR-155-mediated control of HO-1 expression in CD4(+) T cells was shown to sustain in vivo antigen-specific expansion and IL-2 production. Thus, our data identify HO-1 regulation as a mechanism by which miR-155 promotes T-cell-driven inflammation.
authors: Institute for Medical Immunology, Faculty of Medicine, Université Libre de Bruxelles (ULB), Gosselies, Belgium; Department of Clinical Microbiology and Immunology, College of Medical Laboratory Sciences, Third Military Medical University, Chongqing, China.
authors: Jinyu
authors: J
authors: Zhang
authors: Patricia
authors: P
authors: Vandevenne
authors: Haifa
authors: H
authors: Hamdi
authors: Merry
authors: M
authors: Van Puyvelde
authors: Alessandro
authors: A
authors: Zucchi
authors: Marie
authors: M
authors: Bettonville
authors: Kathleen
authors: K
authors: Weatherly
authors: Michel Y
authors: MY
authors: Braun
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000276:immunology*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000276:immunology*; D007108:Immune Tolerance; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000276:immunology
chemical_list: D007376:Interleukin-2; D008565:Membrane Proteins; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: Adaptive tolerance; Heme oxygenase 1 (HO-1); Immunoregulation; Micro-RNA; Th1