title: The nuclear IκB family protein IκBNS influences the susceptibility to experimental autoimmune encephalomyelitis in a murine model.
abstract: 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.
authors.affiliation: Laboratory of Cell Recognition and Response, Tohoku University, Miyagi, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Department of Pathology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
authors.affiliation: Department of Genomic Pathology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Isagawa
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Manabe
authors.affiliation: Laboratory of Immune Regulation, Osaka University, Osaka, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Laboratory of Cell Recognition and Response, Tohoku University, Miyagi, Japan; Department of Cell signaling, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: MaruYama
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3