So far, the pathologic role of innate cells has been reported in many autoimmune diseases, such as SLE, RA, etc. This review suggests that at least two mechanisms involved in the autoreactivity could be exerted by metabolic reprogramming of innate immune cells: (i) direct activation of metabolic pathways, such as glycolysis and mTOR, that induce excessive immune responses, resolving in autoimmune disorders; (ii) an indirect mechanism acting on pDC via the immunocomplex-driven release of IFN-α induced autoimmune diseases. This evidence concerns the gene MTOR and rheumatoid arthritis.