RRC ID 54354
Author Kobayashi S, Hara A, Isagawa T, Manabe I, Takeda K, MaruYama T.
Title The nuclear IκB family protein IκBNS influences the susceptibility to experimental autoimmune encephalomyelitis in a murine model.
Journal PLoS One
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.
Volume 9(10)
Pages e110838
Published 2014-1-1
DOI 10.1371/journal.pone.0110838
PII PONE-D-14-24165
PMID 25347393
PMC PMC4210207
MeSH Animals Cell Differentiation Disease Models, Animal Disease Susceptibility* Encephalomyelitis, Autoimmune, Experimental / genetics Encephalomyelitis, Autoimmune, Experimental / immunology Encephalomyelitis, Autoimmune, Experimental / metabolism* Gene Expression Regulation I-kappa B Proteins / genetics I-kappa B Proteins / metabolism* 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 T-Lymphocyte Subsets / cytology T-Lymphocyte Subsets / immunology T-Lymphocyte Subsets / metabolism Th17 Cells / cytology Th17 Cells / immunology Th17 Cells / metabolism
IF 2.74
Times Cited 20
DNA material pGL4.12-mouse IL-17A promoter (-6647 to +1) (RDB16724) pcDNA3-FLAG-mouse ROR gamma t(RDB16728) pEF6-FLAG-mouse IkappaBNS (RDB16725) pEF6-HA-mouse IkappaBNS (RDB16726) pEF6-Myc-mouse IkappaBNS (RDB16727)