title: Higher susceptibility to experimental autoimmune encephalomyelitis in Muc1-deficient mice is associated with increased Th1/Th17 responses.
abstract: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system in which dendritic cells (DC) play an important role in the development of inflammatory responses. Recently it has been shown that Muc1, a membrane tethered glycoprotein, has an ability to suppress inflammatory responses in cultured DC. The objective of this study was to investigate the possible involvement of Muc1 in the development of MS using experimental autoimmune encephalomyelitis (EAE) in mice, a widely used animal model of MS. Our results showed that: (1) Muc1(-/-) mice developed greater EAE severity compared with wild type (wt) mice, which correlated with increased numbers of Th1 and Th17 cells infiltrating into the CNS; (2) upon stimulation, splenic DC from Muc1(-/-) mice produced greater amounts of IL-1β, IL-6, and IL-12 but less amounts of IL-10 compared with those from wt mice; and (3) the ability of splenic DC to differentiate antigen-specific CD4+ T cells into Th1 and Th17 cells was greater in Muc1(-/-) mice compared with wt mice. We conclude that Muc1 plays an anti-inflammatory role in EAE. This is the first report demonstrating the possible involvement of Muc1 in the development of MS and might provide a potential target for immunotherapy.
authors.affiliation: Department of Microbiology & Immunology and Center for Inflammation, Translational and Clinical Lung Research, Temple University School of Medicine, Philadelphia, PA, United States.
authors.forename: Jui-Hung
authors.initials: JH
authors.lastname: Yen
authors.affiliation: Department of Microbiology & Immunology and Center for Inflammation, Translational and Clinical Lung Research, Temple University School of Medicine, Philadelphia, PA, United States.
authors.forename: Shuyun
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Microbiology & Immunology and Center for Inflammation, Translational and Clinical Lung Research, Temple University School of Medicine, Philadelphia, PA, United States.
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: Park
authors.affiliation: Department of Microbiology & Immunology and Center for Inflammation, Translational and Clinical Lung Research, Temple University School of Medicine, Philadelphia, PA, United States.
authors.forename: Doina
authors.initials: D
authors.lastname: Ganea
authors.affiliation: Department of Microbiology & Immunology and Center for Inflammation, Translational and Clinical Lung Research, Temple University School of Medicine, Philadelphia, PA, United States. Electronic address: kckim@temple.edu.
authors.forename: Kwang Chul
authors.initials: KC
authors.lastname: Kim
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology; D003713:Dendritic Cells / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007378:Interleukins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018396:Mucin-1 / Q000235:genetics* / Q000502:physiology*; D009103:Multiple Sclerosis / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D007378:Interleukins; D018396:Mucin-1