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

Shuhei Kobayashi; Akira Hara; Takayuki Isagawa; Ichiro Manabe; Kiyoshi Takeda; Takashi MaruYama

doi:10.1371/journal.pone.0110838

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

PLoS One. 2014 Oct 27;9(10):e110838. doi: 10.1371/journal.pone.0110838. eCollection 2014.

Authors

Shuhei Kobayashi¹, Akira Hara², Takayuki Isagawa³, Ichiro Manabe⁴, Kiyoshi Takeda⁵, Takashi MaruYama⁶

Affiliations

¹ Laboratory of Cell Recognition and Response, Tohoku University, Miyagi, Japan.
² Department of Pathology, Gifu University Graduate School of Medicine, Gifu, Japan.
³ Department of Genomic Pathology, Tokyo Medical and Dental University, Tokyo, Japan.
⁴ Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.
⁵ Laboratory of Immune Regulation, Osaka University, Osaka, Japan.
⁶ Laboratory of Cell Recognition and Response, Tohoku University, Miyagi, Japan; Department of Cell signaling, Gifu University Graduate School of Medicine, Gifu, Japan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

I-kappa B Proteins
NF-kappa B
Nuclear Receptor Subfamily 1, Group F, Member 3

Grants and funding

This work was supported in part by a Grant-in-Aid for Scientific Research on Innovative Areas (25118702) from the Ministry of Education, a Grant-in-Aid for Young Scientists (B) (24790458) from the Japan Society for the Promotion of Science, and by grants from the Takeda Science Foundation, the Uehara Memorial Foundation, the Novartis Foundation, and the Sumitomo Foundation to TMY. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.