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Sema4A inhibits the therapeutic effect of IFN- in EAE

Koda, T;Okuno, T;Takata, K;Honorat, JA;Kinoshita, M;Tada, S;Moriya, M;Sakoda, S;Mochizuki, H;Kumanogoh, A;Nakatsuji, Y;

Approximately one-third of patients with multiple sclerosis (MS) respond poorly to interferon-beta (IFN-) therapy. Serum Sema4A is increased in MS patients, and those who have high Sema4A do not respond to IFN- therapy. In this study, we investigated whether recombinant Sema4A abrogates the efficacy of IFN- in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Administration of Sema4A concurrently with IFN- diminished the efficacy of IFN- 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-.