title: Cutting edge: T cell Ig mucin-3 reduces inflammatory heart disease by increasing CTLA-4 during innate immunity.
abstract: Autoimmune diseases can be reduced or even prevented if proinflammatory immune responses are appropriately down-regulated. Receptors (such as CTLA-4), cytokines (such as TGF-beta), and specialized cells (such as CD4+CD25+ T regulatory cells) work together to keep immune responses in check. T cell Ig mucin (Tim) family proteins are key regulators of inflammation, providing an inhibitory signal that dampens proinflammatory responses and thereby reducing autoimmune and allergic responses. We show in this study that reducing Tim-3 signaling during the innate immune response to viral infection in BALB/c mice reduces CD80 costimulatory molecule expression on mast cells and macrophages and reduces innate CTLA-4 levels in CD4+ T cells, resulting in decreased T regulatory cell populations and increased inflammatory heart disease. These results indicate that regulation of inflammation in the heart begins during innate immunity and that Tim-3 signaling on cells of the innate immune system critically influences regulation of the adaptive immune response.
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Frisancho-Kiss
authors.forename: Jennifer F
authors.initials: JF
authors.lastname: Nyland
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Davis
authors.forename: Masheka A
authors.initials: MA
authors.lastname: Barrett
authors.forename: Shannon J L
authors.initials: SJ
authors.lastname: Gatewood
authors.forename: Dolores B
authors.initials: DB
authors.lastname: Njoku
authors.forename: Daniela
authors.initials: D
authors.lastname: Cihakova
authors.forename: Ellen K
authors.initials: EK
authors.lastname: Silbergeld
authors.forename: Noel R
authors.initials: NR
authors.lastname: Rose
authors.forename: DeLisa
authors.initials: D
authors.lastname: Fairweather
mesh_terms: D000208:Acute Disease; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D060908:CTLA-4 Antigen; D002465:Cell Movement / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology; D029822:Enterovirus B, Human / Q000276:immunology; D004769:Enterovirus Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D005434:Flow Cytometry; D000072597:Hepatitis A Virus Cellular Receptor 2; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000502:physiology; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009205:Myocarditis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011991:Receptors, Virus / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D018836:Inflammation Mediators; D011991:Receptors, Virus