title: Myosin-primed tolerogenic dendritic cells ameliorate experimental autoimmune myocarditis.
abstract: OBJECTIVE
  Autoimmunity plays an important role in the pathogenesis of viral myocarditis and giant cell myocarditis. Experimental autoimmune myocarditis (EAM) is a mouse model of myocarditis that is induced by cardiac myosin. Tolerogenic dendritic cells (tDCs) are used as anti-inflammatory and immunosuppressive targets in a number of autoimmune disease models, but their effect on EAM has not been addressed. The aim of this study was to investigate whether tDC therapy in an EAM mouse model can suppress inflammatory myocarditis, a potential precursor of dilated cardiomyopathy.
  
  
  RESULTS
  tDCs were generated by treating immature DCs (imDCs) with TNF-α and cardiac myosin. Mice with EAM were injected twice with tDCs (with a 1-week interval) at three doses (2 × 10(5), 1 × 10(6), or 2 × 10(6)). The severity of myocarditis was histopathologically assessed. The phenotypes of the DC and regulatory T (Treg) cell populations were determined by flow cytometry and the effect of tDCs on autoimmunity-inducing cytokines was examined by ELISA. Myosin-pulsed tDCs displayed lower levels of DC-related surface markers and expressed higher levels of indoleamine 2, 3-dioxygenase (IDO) than mature DCs (mDCs). Histopathological examination revealed that hearts from tDC-treated mice showed markedly reduced myocardial inflammation compared with those of untreated EAM mice. These therapeutic effects by tDCs were mediated at least by enhanced myosin-specific Treg cell induction and anti-inflammatory cytokine secretion.
  
  
  CONCLUSIONS
  Taken together, these results show for the first time that myosin-pulsed tDCs ameliorate EAM, and that this occurs most likely via the induction of antigen-specific Treg cells.
authors.affiliation: Department of Biotechnology, CHA University, 222 Yatap-Dong, Bundang-gu, Seongnam, Gyeonggi-do 463-836, Republic of Korea.
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Kim
authors.forename: Hyo Eun
authors.initials: HE
authors.lastname: Park
authors.forename: Eun Gae
authors.initials: EG
authors.lastname: Lee
authors.forename: Nam-Chul
authors.initials: NC
authors.lastname: Jung
authors.forename: Jie-Young
authors.initials: JY
authors.lastname: Song
authors.forename: Han Geuk
authors.initials: HG
authors.lastname: Seo
authors.forename: Ki-Bae
authors.initials: KB
authors.lastname: Seung
authors.forename: Kiyuk
authors.initials: K
authors.lastname: Chang
authors.forename: Dae-Seog
authors.initials: DS
authors.lastname: Lim
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015551:Autoimmunity; D024722:Cardiac Myosins / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D004195:Disease Models, Animal; D007108:Immune Tolerance; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013997:Time Factors; D014611:Vaccination
chemical_list: D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D018836:Inflammation Mediators; D024722:Cardiac Myosins
keywords: Experimental autoimmune myocarditis; Myosin; Regulatory T cells; Tolerogenic dendritic cells