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The Role of Reactive Oxygen Species in Animal Models of Autoimmunity

Hultqvist, Malin LU (2007) In Lund University Faculty of Medicine Doctoral Dissertation Series 2007:176.
Abstract
Reactive oxygen species (ROS) produced by the phagocyte NADPH oxidase complex are important in the killing of invading pathogens. Lately, a role of ROS has been suggested in regulation of the immune system. This was further highlighted when the Ncf1 gene, encoding a subunit of the NADPH oxidase complex, was found to regulate arthritis severity in rats. Interestingly, the fact that increased arthritis susceptibility was mediated by a lowered ROS production diverged from the general dogma that ROS in general promotes inflammation. The studies included in this thesis aimed to further investigate and characterize the influence of Ncf1 and ROS in autoimmune diseases such as arthritis and encephalomyelitis. By using animal models of the human... (More)
Reactive oxygen species (ROS) produced by the phagocyte NADPH oxidase complex are important in the killing of invading pathogens. Lately, a role of ROS has been suggested in regulation of the immune system. This was further highlighted when the Ncf1 gene, encoding a subunit of the NADPH oxidase complex, was found to regulate arthritis severity in rats. Interestingly, the fact that increased arthritis susceptibility was mediated by a lowered ROS production diverged from the general dogma that ROS in general promotes inflammation. The studies included in this thesis aimed to further investigate and characterize the influence of Ncf1 and ROS in autoimmune diseases such as arthritis and encephalomyelitis. By using animal models of the human Rheumatoid Arthritis (RA) and Multiple Sclerosis (MS), we could confirm the importance of decreased ROS production in development of autoimmunity. This was validated by identification of a mouse Ncf1 mutation that also decreased ROS production and resulted in enhanced arthritis. In addition, we found that T cell reactivity was altered in animals with impaired ROS production, presumably through interaction with antigen presenting cells. We found that the redox level on T cell membranes was the determinant for arthritogenicity. Interestingly, we could also reverse the genetic effect by administrate NADPH oxidase activating oils into rats, thereby preventing and ameliorating disease. This is promising as these findings provide a novel pathway to target therapeutically in complex inflammatory diseases. In summary, this thesis describes a pathway in the pathology of arthritis and encephalomyelitis that reveals a new way to treat autoimmunity. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Prof Hawkins, Philip, The Babraham Institute, Babraham Research Campus, Cambridge, UK
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Mice, Phytol, ROS, NOX, NADPH, p47phox, Ncf1, EAE, inflammation, Arthritis, RA, MS, Rats, Autoimmunity
in
Lund University Faculty of Medicine Doctoral Dissertation Series
volume
2007:176
publisher
Department of Experimental Medical Science, Lund Univeristy
defense location
GK Lecture Hall, Biomedical Center, Lund
defense date
2007-12-14 09:00
ISSN
1652-8220
ISBN
978-91-85897-54-4
language
English
LU publication?
yes
id
ecf5c3ea-5e19-4ded-95c6-c98bcc06a713 (old id 618498)
date added to LUP
2007-11-23 12:14:09
date last changed
2016-09-19 08:44:59
@phdthesis{ecf5c3ea-5e19-4ded-95c6-c98bcc06a713,
  abstract     = {Reactive oxygen species (ROS) produced by the phagocyte NADPH oxidase complex are important in the killing of invading pathogens. Lately, a role of ROS has been suggested in regulation of the immune system. This was further highlighted when the Ncf1 gene, encoding a subunit of the NADPH oxidase complex, was found to regulate arthritis severity in rats. Interestingly, the fact that increased arthritis susceptibility was mediated by a lowered ROS production diverged from the general dogma that ROS in general promotes inflammation. The studies included in this thesis aimed to further investigate and characterize the influence of Ncf1 and ROS in autoimmune diseases such as arthritis and encephalomyelitis. By using animal models of the human Rheumatoid Arthritis (RA) and Multiple Sclerosis (MS), we could confirm the importance of decreased ROS production in development of autoimmunity. This was validated by identification of a mouse Ncf1 mutation that also decreased ROS production and resulted in enhanced arthritis. In addition, we found that T cell reactivity was altered in animals with impaired ROS production, presumably through interaction with antigen presenting cells. We found that the redox level on T cell membranes was the determinant for arthritogenicity. Interestingly, we could also reverse the genetic effect by administrate NADPH oxidase activating oils into rats, thereby preventing and ameliorating disease. This is promising as these findings provide a novel pathway to target therapeutically in complex inflammatory diseases. In summary, this thesis describes a pathway in the pathology of arthritis and encephalomyelitis that reveals a new way to treat autoimmunity.},
  author       = {Hultqvist, Malin},
  isbn         = {978-91-85897-54-4},
  issn         = {1652-8220},
  keyword      = {Mice,Phytol,ROS,NOX,NADPH,p47phox,Ncf1,EAE,inflammation,Arthritis,RA,MS,Rats,Autoimmunity},
  language     = {eng},
  publisher    = {Department of Experimental Medical Science, Lund Univeristy},
  school       = {Lund University},
  series       = {Lund University Faculty of Medicine Doctoral Dissertation Series},
  title        = {The Role of Reactive Oxygen Species in Animal Models of Autoimmunity},
  volume       = {2007:176},
  year         = {2007},
}