Involvement of Sema4A in the progression of experimental autoimmune myocarditis.
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.
Makino
Nobuhiko
N
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
Toyofuku
Toshihiko
T
Takegahara
Noriko
N
Takamatsu
Hyota
H
Okuno
Tatsusada
T
Nakagawa
Yukinobu
Y
Kang
Sujin
S
Nojima
Satoshi
S
Hori
Masatsugu
M
Kikutani
Hitoshi
H
Kumanogoh
Atsushi
A
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
C534721:Sema4A protein, mouse; D039961:Semaphorins