Autoimmunity is a type I interferon-deficiency syndrome corrected by ingested type IIFN via the GALT system

Type I interferons (IFN-alpha/beta), products of the innate immune system, can modulate immune function whereas proinflammatory IFN-gamma (type II IFN ), a product of the acquired immune system upregulates inflammation smd enh ances cell mediated immunity. We have proposed a unifying hypothesis of the origin of autoimmunity as a type I IFN immunodeficiency syndrome involving inadequate regulation of the acquired immune system product IFN-gamma by t he IFN-alpha/beta innate immune system. The common theme of ingested type I IFNs in autoimmunity is inhibition of proinflammatory type II IFN systemic ally or at the target organ. In multiple sclerosis (MS) and insulin-depende nt diabetes mellitus (IDDM) at the target organ, and in rheumatoid arthriti s (RA) as a regulator of other proinflammatory cytokines, IFN-gamma is the nexus of inflammation in autoimmunity.. Ingested type I IFNs counteract typ e II IFN, overcome the relative lack of type I IFN activity, and ameliorate autoimmunity. The administration of type I IFNs (IFN-alpha/beta) via the g ut offers an exciting alternative to systemic application for overcoming th e type I IFN immunodeficiency in autoimmunity. Successful rise of ingested type I IFN in three separate prototypical autoimmune diseases suggests a br oad antiinflammatory therapeutic profile for this technology.