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Lack of Reactive Oxygen Species Breaks T Cell Tolerance to Collagen Type II and Allows Development of Arthritis in Mice.

Hultqvist, Malin LU ; Bäcklund, Johan LU ; Bauer, Kristin LU ; Gelderman, Kyra LU and Holmdahl, Rikard LU (2007) In Journal of Immunology 179(3). p.1431-1437
Abstract
The view on reactive oxygen species (ROS) in inflammation is currently shifting from being considered damaging toward having a more complex role in regulating inflammatory reactions. We recently demonstrated a role of ROS in regulation of animal models for the autoimmune disease rheumatoid arthritis. Low levels of ROS production, due to a mutation in the Ncf1 gene coding for the Ncf1 (alias p47phox) subunit of the NADPH oxidase complex, was shown to be associated with increased autoimmunity and arthritis severity in both rats and mice. To further investigate the role of ROS in autoimmunity, we studied transgenic mice expressing collagen type II (CII) with a mutation (D266E) in the immunodominant epitope that mimics the rat and human CII... (More)
The view on reactive oxygen species (ROS) in inflammation is currently shifting from being considered damaging toward having a more complex role in regulating inflammatory reactions. We recently demonstrated a role of ROS in regulation of animal models for the autoimmune disease rheumatoid arthritis. Low levels of ROS production, due to a mutation in the Ncf1 gene coding for the Ncf1 (alias p47phox) subunit of the NADPH oxidase complex, was shown to be associated with increased autoimmunity and arthritis severity in both rats and mice. To further investigate the role of ROS in autoimmunity, we studied transgenic mice expressing collagen type II (CII) with a mutation (D266E) in the immunodominant epitope that mimics the rat and human CII (i.e., mutated mouse collagen or MMC). This mutation results in a stronger binding of the epitope to the MHC class II molecule and leads to more pronounced tolerance and resistance to arthritis induced with rat CII. When the Ncf1 mutation was bred into these mice, tolerance was broken, resulting in enhanced T cell autoreactivity, high titers of anti-CII Abs, and development of severe arthritis. These findings highlight the importance of a sufficient ROS production in maintenance of tolerance to self-Ags, a central mechanism in autoimmune diseases such as rheumatoid arthritis. This is important as we, for the first time, can follow the effect of ROS on molecular mechanisms where T cells are responsible for either protection or promotion of arthritis depending on the level of oxygen species produced. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Reactive Oxygen, T Cell Tolerance, Collagen Type II
in
Journal of Immunology
volume
179
issue
3
pages
1431 - 1437
publisher
American Association of Immunologists
external identifiers
  • wos:000248319700005
  • scopus:34548657163
ISSN
1550-6606
language
English
LU publication?
yes
id
21ace3c6-4b80-4e48-9758-800f6fe848a5 (old id 540611)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17641008&dopt=Abstract
date added to LUP
2007-12-12 09:26:17
date last changed
2017-11-19 04:07:13
@article{21ace3c6-4b80-4e48-9758-800f6fe848a5,
  abstract     = {The view on reactive oxygen species (ROS) in inflammation is currently shifting from being considered damaging toward having a more complex role in regulating inflammatory reactions. We recently demonstrated a role of ROS in regulation of animal models for the autoimmune disease rheumatoid arthritis. Low levels of ROS production, due to a mutation in the Ncf1 gene coding for the Ncf1 (alias p47phox) subunit of the NADPH oxidase complex, was shown to be associated with increased autoimmunity and arthritis severity in both rats and mice. To further investigate the role of ROS in autoimmunity, we studied transgenic mice expressing collagen type II (CII) with a mutation (D266E) in the immunodominant epitope that mimics the rat and human CII (i.e., mutated mouse collagen or MMC). This mutation results in a stronger binding of the epitope to the MHC class II molecule and leads to more pronounced tolerance and resistance to arthritis induced with rat CII. When the Ncf1 mutation was bred into these mice, tolerance was broken, resulting in enhanced T cell autoreactivity, high titers of anti-CII Abs, and development of severe arthritis. These findings highlight the importance of a sufficient ROS production in maintenance of tolerance to self-Ags, a central mechanism in autoimmune diseases such as rheumatoid arthritis. This is important as we, for the first time, can follow the effect of ROS on molecular mechanisms where T cells are responsible for either protection or promotion of arthritis depending on the level of oxygen species produced.},
  author       = {Hultqvist, Malin and Bäcklund, Johan and Bauer, Kristin and Gelderman, Kyra and Holmdahl, Rikard},
  issn         = {1550-6606},
  keyword      = {Reactive Oxygen,T Cell Tolerance,Collagen Type II},
  language     = {eng},
  number       = {3},
  pages        = {1431--1437},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Lack of Reactive Oxygen Species Breaks T Cell Tolerance to Collagen Type II and Allows Development of Arthritis in Mice.},
  volume       = {179},
  year         = {2007},
}