We previously showed that the sustained inflammatory microenvironment associated with inflammatory/demyelinating diseases leads to a local dysregulation of T3 metabolism, directly mediated by the inflammatory cytokines, which increase the expression of DIO3, the T3-inactivating enzyme, and down-regulate the TRs, thus blocking the activation of the differentiation machinery [26,27,33]. Here, DIO3 is linked to demyelinating disease.