The Nuclear IκB Family Protein IκB(NS) Influences the Susceptibility to Experimental Autoimmune Encephalomyelitis in a Murine Model

The nuclear IκB family protein IκB(NS) is expressed in T cells and plays an important role in Interferon (IFN)-γ and Interleukin (IL)-2 production. IκB-ζ, the most similar homolog of IκB(NS), plays an important role in the generation of T helper (Th)17 cells in cooperation with RORγt, a master regulator of Th17 cells. Thus, IκB-ζ deficient mice are resistant to Th17-dependent experimental autoimmune encephalomyelitis (EAE). However, IκB-ζ deficient mice develop the autoimmune-like Sjögren syndrome with aging. Here we found that IκB(NS)-deficient (Nfkbid(−/−)) mice show resistance against developing Th17-dependent EAE. We found that Nfkbid(−/−) T cells have decreased expression of IL-17-related genes and RORγt in response to Transforming Growth Factor (TGF)-β1 and IL-6 stimulation. Thus, IκB(NS) plays a pivotal role in the generation of Th17 cells and in the control of Th17-dependent EAE.