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Involvement of Sema4A in the progression of experimental autoimmune myocarditis |
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| Authors: | Makino Nobuhiko Toyofuku Toshihiko Takegahara Noriko Takamatsu Hyota Okuno Tatsusada Nakagawa Yukinobu Kang Sujin Nojima Satoshi Hori Masatsugu Kikutani Hitoshi Kumanogoh Atsushi |
| Affiliation: | a Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan b Department of Immunopathology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan c World Premier International Immunology Frontier Research Center, Osaka University, 3-1 Ymada-oka, Suita, Osaka 565-0871, Japan d Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan e Department of Dermatology, Osaka University Graduate School of Medicine, 2-2Yamadoka, Suita, Osaka 565-087, Japan f Department of Pathology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan g CREST, Japan Science and Technology Corporation, Japan h Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan |
| 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-α 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. |
| Keywords: | DCM, dilated cardiomyopathy SCID, severe combined immunodeficiency EAM, experimental autoimmune myocarditis MyHC-α, myosin α heavy chain DCs, dendritic cells IFN-γ, Interferon-γ TH1, type 1 helper T-cells IL, interleukin Tim-2, T-cell, immunoglobulin and mucin domain protein 2 EAE, experimental autoimmune encephalomyelitis Treg, regulatory T-cells Foxp3, forkhead box P3 |
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