Figure 2.

The impact of NF-κB on MS animal models. The effects of nuclear factor-κB (NF-κB) on experimental autoimmune encephalomyelitis (EAE) and cuprizone models are summarized as follows. c-Rel and IKKβ in macrophages/microglia might influence the production of pro-inflammatory cytokines/chemokines, M1 macrophage/microglia phenotype polarization, and T cell immune responses. The deficiency of IKKβ in oligodendrocytes does not alter myelin formation, demyelination, and remyelination; however, blocking RelB and the canonical pathway results in a decreased number of mature oligodendrocytes. NF-κB1 and the canonical pathway are required to augment local inflammation through driving the production of pro-inflammatory mediators and suppressing the levels of neuroprotective molecule adhesion molecules and CD8+ CD122+ regulatory T cells (Tregs). Neuronal IKKβ has been suggested to suppress CNS inflammation. By contrast, conditional deletion of the neuronal NF-κB pathway by the transgenic expression of an IκBα super-repressor did not influence the EAE course. c-Rel is essential in Treg, T helper 1 (Th1), and Th17 differentiation. In addition to c-Rel, Th1 differentiation is also regulated by RelB, whereas NF-κB1 is essential in mediating Th2 responses.