title: PD-1 deletion restores susceptibility to experimental autoimmune encephalomyelitis in miR-155-deficient mice.
abstract: MiR-155 (-/-) mice are highly resistant to experimental autoimmune encephalomyelitis (EAE), while Pdcd1 (-/-) mice develop a more severe form of the disease. To determine the conflicting roles of these two molecules in the disease, we generated miR-155 (-/-) Pdcd1 (-/-) double knockout (DKO) mice. We found that ablation of programmed cell death protein 1 (PD-1) expression in miR-155-deficient mice restored the susceptibility to EAE. The increased severity of the disease in DKO mice was accompanied by an enhanced T-cell infiltration into the brain as well as an increased production of pro-inflammatory cytokines IFN-γ and IL-17. Furthermore, the major contribution of the DKO to EAE was T-cell intrinsic since adoptive transfer of CD4(+) T cells from DKO donors promoted the disease in lymphopenic recipients. These results define PD-1 deficiency in miR-155 (-/-) mice as a promoting factor of autoimmune inflammation by increasing antigen-driven T-cell expansion and infiltration.
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies 1420, Belgium Department of Clinical Microbiology and Immunology, College of Medical Laboratory Science, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies 1420, Belgium mbraun@ulb.ac.be.
authors.forename: Michel Y
authors.initials: MY
authors.lastname: Braun
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D002465:Cell Movement; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D061026:Programmed Cell Death 1 Receptor / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D012720:Severity of Illness Index; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology / Q000473:pathology
chemical_list: D020381:Interleukin-17; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D063308:Myelin-Oligodendrocyte Glycoprotein; C491383:Pdcd1 protein, mouse; D010446:Peptide Fragments; D061026:Programmed Cell Death 1 Receptor; C445081:myelin oligodendrocyte glycoprotein (35-55); D007371:Interferon-gamma
keywords: IFN-γ; IL-17; autoimmunity; inflammation; microRNA