Multiple sclerosis(MS)is a demyelinating autoimmune disease of the central nervous system(CNS).We have shown that oral administration of Bowman-Birk inhibitor(BBI),a soybean-derived serine protease inhibitor,suppresse...Multiple sclerosis(MS)is a demyelinating autoimmune disease of the central nervous system(CNS).We have shown that oral administration of Bowman-Birk inhibitor(BBI),a soybean-derived serine protease inhibitor,suppresses disease in experimental autoimmune encephalomyelitis(EAE),1 a model of MS.We show here that the suppression is dependent on stimulator of interferon genes(STING)and the production of interferon-β(IFN-β)by F4/80+macrophages.Furthermore,we show that the absence of type I IFN receptor-α(IFNAR1)in myeloid cells precludes EAE suppression by BBI,demonstrating that IFN-βsignaling in these cells is relevant for the beneficial effect of BBI.BBI also induces IFN-βproduction by human macrophages and monocytes in a STING-dependent manner,suggesting that BBI could have a therapeutic effect in MS similar to the one in EAE.展开更多
基金supported by a grant from the National Institutes of Health(5R01AI106026)to A.R.
文摘Multiple sclerosis(MS)is a demyelinating autoimmune disease of the central nervous system(CNS).We have shown that oral administration of Bowman-Birk inhibitor(BBI),a soybean-derived serine protease inhibitor,suppresses disease in experimental autoimmune encephalomyelitis(EAE),1 a model of MS.We show here that the suppression is dependent on stimulator of interferon genes(STING)and the production of interferon-β(IFN-β)by F4/80+macrophages.Furthermore,we show that the absence of type I IFN receptor-α(IFNAR1)in myeloid cells precludes EAE suppression by BBI,demonstrating that IFN-βsignaling in these cells is relevant for the beneficial effect of BBI.BBI also induces IFN-βproduction by human macrophages and monocytes in a STING-dependent manner,suggesting that BBI could have a therapeutic effect in MS similar to the one in EAE.
