Sema4A inhibits the therapeutic effect of IFN-β in EAE.
Approximately one-third of patients with multiple sclerosis (MS) respond poorly to interferon-beta (IFN-β) therapy. Serum Sema4A is increased in MS patients, and those who have high Sema4A do not respond to IFN-β therapy. In this study, we investigated whether recombinant Sema4A abrogates the efficacy of IFN-β in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Administration of Sema4A concurrently with IFN-β diminished the efficacy of IFN-β in EAE. These effects of Sema4A were attributed to promote Th1 and Th17 differentiation and to increase adhesive activation of T cells to endothelial cells, even in the presence of IFN-β.
Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Toru
T
Koda
Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Electronic address: okuno@neurol.med.osaka-u.ac.jp.
Tatsusada
T
Okuno
Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Kazushiro
K
Takata
Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Josephe Archie
JA
Honorat
Department of Immune Regulation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Makoto
M
Kinoshita
Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Satoru
S
Tada
Department of Neurology, Toyonaka Municipal Hospital, Toyonaka, Osaka, Japan.
Masayuki
M
Moriya
Department of Neurology, National Hospital Organization Toneyama National Hospital, Toyonaka, Osaka, Japan.
Saburo
S
Sakoda
Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Hideki
H
Mochizuki
Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Atsushi
A
Kumanogoh
Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Electronic address: yuji@neurol.med.osaka-u.ac.jp.
Yuji
Y
Nakatsuji
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D004351:Drug Resistance; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D039961:Semaphorins / Q000378:metabolism* / Q000494:pharmacology
D007155:Immunologic Factors; C534721:Sema4A protein, mouse; D039961:Semaphorins; D016899:Interferon-beta
Experimental autoimmune encephalomyelitis (EAE); Interferon-beta (IFN-β); Multiple sclerosis (MS); Sema4A