The nuclear IκB family protein IκBNS influences the susceptibility to experimental autoimmune encephalomyelitis in a murine model

• Published in: PloS one 2014-10, Vol.9 (10), p.e110838-e110838
• Main Authors: Kobayashi, Shuhei, Hara, Akira, Isagawa, Takayuki, Manabe, Ichiro, Takeda, Kiyoshi, MaruYama, Takashi
• Format: Article
• Language: English
• Subjects: Aging; Animal models; Animals; Biology and Life Sciences; Cell Differentiation; Chemotherapy; Cytokines; Deoxyribonucleic acid; Disease Models, Animal; Disease Susceptibility; DNA; Encephalomyelitis, Autoimmune, Experimental - genetics; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - metabolism; Experimental allergic encephalomyelitis; Gene expression; Gene Expression Regulation; Helper cells; Homology; I-kappa B Proteins - genetics; I-kappa B Proteins - metabolism; Immunoglobulins; Interferon; Interleukin 17; Interleukin 6; Laboratory animals; Lymphocytes; Lymphocytes T; Medicine; Mice; Mice, Knockout; NF-kappa B - genetics; Nuclear Receptor Subfamily 1, Group F, Member 3 - genetics; Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism; Proteins; Sjogren's syndrome; T cell receptors; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Th17 Cells - cytology; Th17 Cells - immunology; Th17 Cells - metabolism; Transforming growth factor; Transforming growth factor-b1
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0110838

The nuclear IκB family protein IκBNS 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 IκBNS, 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 IκBNS-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, IκBNS plays a pivotal role in the generation of Th17 cells and in the control of Th17-dependent EAE.