PMID- 25261487
OWN - NLM
STAT- MEDLINE
DCOM- 20150303
LR  - 20231213
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 193
IP  - 9
DP  - 2014 Nov 1
TI  - NF-kappaB-inducing kinase in thymic stroma establishes central tolerance by 
      orchestrating cross-talk with not only thymocytes but also dendritic cells.
PG  - 4356-67
LID - 10.4049/jimmunol.1400389 [doi]
AB  - Essential roles of NF-kappaB-inducing kinase (NIK) for the development of medullary 
      thymic epithelial cells (mTECs) and regulatory T cells have been highlighted by 
      studies using a strain of mouse bearing a natural mutation of the NIK gene (aly 
      mice). However, the exact mechanisms underlying the defect in thymic cross-talk 
      leading to the breakdown of self-tolerance in aly mice remain elusive. In this 
      study, we demonstrated that production of regulatory T cells and the final 
      maturation process of positively selected conventional alphabeta T cells are impaired in 
      aly mice, partly because of a lack of mature mTECs. Of note, numbers of thymic 
      dendritic cells and their expression of costimulatory molecules were also 
      affected in aly mice in a thymic stroma-dependent manner. The results suggest a 
      pivotal role of NIK in the thymic stroma in establishing self-tolerance by 
      orchestrating cross-talk between mTECs and dendritic cells as well as thymocytes. 
      In addition, we showed that negative selection was impaired in aly mice as a 
      result of the stromal defect, which accounts for the development of 
      organ-specific autoimmunity through a lack of normal NIK.
CI  - Copyright (c) 2014 by The American Association of Immunologists, Inc.
FAU - Mouri, Yasuhiro
AU  - Mouri Y
AD  - Division of Molecular Immunology, Institute for Enzyme Research, University of 
      Tokushima, Tokushima 770-8503, Japan; and.
FAU - Nishijima, Hitoshi
AU  - Nishijima H
AD  - Division of Molecular Immunology, Institute for Enzyme Research, University of 
      Tokushima, Tokushima 770-8503, Japan; and.
FAU - Kawano, Hiroshi
AU  - Kawano H
AD  - Division of Molecular Immunology, Institute for Enzyme Research, University of 
      Tokushima, Tokushima 770-8503, Japan; and.
FAU - Hirota, Fumiko
AU  - Hirota F
AD  - Division of Molecular Immunology, Institute for Enzyme Research, University of 
      Tokushima, Tokushima 770-8503, Japan; and.
FAU - Sakaguchi, Nobuo
AU  - Sakaguchi N
AD  - Department of Immunology, Graduate School of Life Sciences, Kumamoto University, 
      Kumamoto 860-8556, Japan.
FAU - Morimoto, Junko
AU  - Morimoto J
AD  - Division of Molecular Immunology, Institute for Enzyme Research, University of 
      Tokushima, Tokushima 770-8503, Japan; and.
FAU - Matsumoto, Mitsuru
AU  - Matsumoto M
AD  - Division of Molecular Immunology, Institute for Enzyme Research, University of 
      Tokushima, Tokushima 770-8503, Japan; and mitsuru@ier.tokushima-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140926
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (B7-1 Antigen)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - B7-1 Antigen/metabolism
MH  - Cell Communication/*immunology
MH  - Cell Differentiation
MH  - Dendritic Cells/*immunology/metabolism
MH  - Epithelial Cells/metabolism
MH  - Gene Expression
MH  - Immunophenotyping
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Models, Immunological
MH  - Mutation
MH  - Phenotype
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - Receptors, Antigen, T-Cell, alpha-beta/metabolism
MH  - Self Tolerance/*immunology
MH  - Stromal Cells/metabolism
MH  - T-Lymphocytes, Regulatory/cytology/immunology/metabolism
MH  - Thymocytes/*immunology/metabolism
MH  - Thymus Gland/immunology/metabolism
MH  - NF-kappaB-Inducing Kinase
EDAT- 2014/09/28 06:00
MHDA- 2015/03/04 06:00
CRDT- 2014/09/28 06:00
PHST- 2014/09/28 06:00 [entrez]
PHST- 2014/09/28 06:00 [pubmed]
PHST- 2015/03/04 06:00 [medline]
AID - jimmunol.1400389 [pii]
AID - 10.4049/jimmunol.1400389 [doi]
PST - ppublish
SO  - J Immunol. 2014 Nov 1;193(9):4356-67. doi: 10.4049/jimmunol.1400389. Epub 2014 
      Sep 26.