title: Involvement of Sema4A in the progression of experimental autoimmune myocarditis.
abstract: Dilated cardiomyopathy often results from autoimmunity triggered by microbial infections during myocarditis. However, it remains unclear how immunological disorders are implicated in pathogenesis of autoimmune myocarditis. Here, we demonstrated that Sema4A, a class IV semaphorin, plays key roles in experimental autoimmune myocarditis (EAM). Dendritic cells pulsed with myosin heavy chain-alpha peptides induced severe myocarditis in wild-type mice, but not in Sema4A-deficient mice. In adoptive transfer experiments, CD4+ T-cells from wild-type mice induced severe myocarditis, while CD4+ T-cells from Sema4A-deficient mice exhibited considerably attenuated myocarditis. Our results indicated that Sema4A is critically involved in EAM by regulating differentiation of T-cells.
authors.affiliation: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Makino
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Toyofuku
authors.forename: Noriko
authors.initials: N
authors.lastname: Takegahara
authors.forename: Hyota
authors.initials: H
authors.lastname: Takamatsu
authors.forename: Tatsusada
authors.initials: T
authors.lastname: Okuno
authors.forename: Yukinobu
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Sujin
authors.initials: S
authors.lastname: Kang
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nojima
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kikutani
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumanogoh
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002454:Cell Differentiation / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D004198:Disease Susceptibility; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology; D039961:Semaphorins / Q000235:genetics / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology
chemical_list: C534721:Sema4A protein, mouse; D039961:Semaphorins