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Ncf1-Associated Reduced Oxidative Burst Promotes IL-33R+ T Cell-Mediated Adjuvant-Free Arthritis in Mice.

Hagenow, Kristin; Gelderman, Kyra LU ; Hultqvist, Malin LU ; Merky, Patrick LU ; Bäcklund, Johan LU ; Frey, Oliver; Kamradt, Thomas and Holmdahl, Rikard LU (2009) In Journal of Immunology 183(2). p.874-881
Abstract
Reactive oxygen species (ROS) are important in the immune defense against invading pathogens, but they are also key molecules in the regulation of inflammatory reactions. Low levels of ROS production due to a polymorphism in the neutrophil cytosolic factor 1 (Ncf1) gene are associated with autoimmunity and arthritis severity in mouse models induced with adjuvant. We established an adjuvant-free arthritis model in which disease is induced by injection of the autoantigen collagen type II (CII) and depends on IL-5-producing T cells and eosinophils. In addition, the transgenic expression of mutated mouse CII allowed us to investigate an autoreactive immune response to an autologous Ag and by that natural tolerance mechanism. We show that a... (More)
Reactive oxygen species (ROS) are important in the immune defense against invading pathogens, but they are also key molecules in the regulation of inflammatory reactions. Low levels of ROS production due to a polymorphism in the neutrophil cytosolic factor 1 (Ncf1) gene are associated with autoimmunity and arthritis severity in mouse models induced with adjuvant. We established an adjuvant-free arthritis model in which disease is induced by injection of the autoantigen collagen type II (CII) and depends on IL-5-producing T cells and eosinophils. In addition, the transgenic expression of mutated mouse CII allowed us to investigate an autoreactive immune response to an autologous Ag and by that natural tolerance mechanism. We show that a deficient ROS production, due to a spontaneous mutation in Ncf1, leads to increased autoantibody production and expansion of IL-33R-expressing T cells, impaired T cell tolerance toward tissue-specific CII, and severe arthritis in this unique model without disturbing adjuvant effects. These results demonstrate that the insufficient production of ROS promotes the breakdown of immune tolerance and development of autoimmune and adjuvant-free arthritis through an IL-5- and IL33R-dependent T cell activation pathway. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
183
issue
2
pages
874 - 881
publisher
American Association of Immunologists
external identifiers
  • wos:000267812600012
  • pmid:19553535
  • scopus:70249106454
ISSN
1550-6606
DOI
10.4049/jimmunol.0900966
language
English
LU publication?
yes
id
2e54ac68-ea2e-4a68-aa90-fb84bc10d63e (old id 1433900)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19553535?dopt=Abstract
date added to LUP
2009-07-06 09:16:17
date last changed
2017-08-27 03:49:14
@article{2e54ac68-ea2e-4a68-aa90-fb84bc10d63e,
  abstract     = {Reactive oxygen species (ROS) are important in the immune defense against invading pathogens, but they are also key molecules in the regulation of inflammatory reactions. Low levels of ROS production due to a polymorphism in the neutrophil cytosolic factor 1 (Ncf1) gene are associated with autoimmunity and arthritis severity in mouse models induced with adjuvant. We established an adjuvant-free arthritis model in which disease is induced by injection of the autoantigen collagen type II (CII) and depends on IL-5-producing T cells and eosinophils. In addition, the transgenic expression of mutated mouse CII allowed us to investigate an autoreactive immune response to an autologous Ag and by that natural tolerance mechanism. We show that a deficient ROS production, due to a spontaneous mutation in Ncf1, leads to increased autoantibody production and expansion of IL-33R-expressing T cells, impaired T cell tolerance toward tissue-specific CII, and severe arthritis in this unique model without disturbing adjuvant effects. These results demonstrate that the insufficient production of ROS promotes the breakdown of immune tolerance and development of autoimmune and adjuvant-free arthritis through an IL-5- and IL33R-dependent T cell activation pathway.},
  author       = {Hagenow, Kristin and Gelderman, Kyra and Hultqvist, Malin and Merky, Patrick and Bäcklund, Johan and Frey, Oliver and Kamradt, Thomas and Holmdahl, Rikard},
  issn         = {1550-6606},
  language     = {eng},
  number       = {2},
  pages        = {874--881},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Ncf1-Associated Reduced Oxidative Burst Promotes IL-33R+ T Cell-Mediated Adjuvant-Free Arthritis in Mice.},
  url          = {http://dx.doi.org/10.4049/jimmunol.0900966},
  volume       = {183},
  year         = {2009},
}