Matches in SemOpenAlex for { <https://semopenalex.org/work/W1755667245> ?p ?o ?g. }
- W1755667245 abstract "The production of reactive oxygen species (ROS) through a process called oxidative burst is an essential defence mechanism against pathogens. In phagocytes, such as neutrophils and macrophages, the NADPH oxidase 2 (NOX2) complex is the main source of ROS. Genetic alterations in any of the components of the NOX2 complex that impair the ROS production are at the origin of a condition called chronic granulomatous disease (CGD), characterized by recurrent life threatening bacterial and fungal infections. Recently, natural occurring mutations in Ncf1, a regulatory component of the NOX2 complex, were described to compromise the protein function and to increase arthritis severity in rats and mice. Macrophages are phagocytes that express NCF1 and are able to kill pathogens. At the same time, they are antigenpresenting cells known to play an important role in arthritis. We therefore hypothesized that expression of NCF1 in macrophages would have an impact on the immune response during arthritis and bacterial infections. The aim of the studies presented in this thesis is to evaluate the influence of NCF1 expressed by macrophages on development of arthritis and resolution of bacterial infections. Using transgenic mouse models we could describe a role for macrophages in both priming and activation of arthritogenic T cells. In a first transgenic mouse, expression of functional NCF1 restricted to macrophages reduced arthritis severity, priming of Th1 T cells and T cell proliferation, therefore limiting the T cell-dependent autoimmune outbreak. In a second transgenic mouse strain, where macrophages were the only cells expressing the arthritis-prone MHC class II A molecule, macrophages could prime arthritogenic T cells and mediate arthritis development, but only in NCF1 deficient setting. We could conclude that ROS production by macrophages is important in determining the activation state of T cells and in regulating the severity of arthritis. As in the human CGD situation, mice carrying the Ncf1 mutation were more susceptible to spontaneous and induced bacterial infections. Using the transgenic mouse where macrophages expressed the functional NCF1, we observed that macrophage-derived ROS effectively protected mice from bacterial infections, a function believed to be executed mainly by neutrophils. Finally, we tested a new model of arthritis where the disease was induced with a peptide of a glycolytic enzyme. We found that the symptoms and pathogenesis of the disease resembled the one of the most common arthritis model, collagen-induced arthritis, which is induced with the full collagen protein. Both diseases are dependent on an intact adaptive immune system and their severity is influenced by Ncf1. We were also able to identify one of the important residues causing the peptide’s arthritogenicity. In summary, our data highlight the crucial role of NCF1, and consequently of NOX2 complex, in regulating both innate and adaptive immune responses. NCF1-dependent ROS in macrophages was important during both phagocytosis and antigen presentation, resulting in clearance of bacterial infection and suppression of chronic inflammation. These findings will facilitate further investigations of the molecular pathways through which ROS influence arthritis pathogenesis and hopefully lead to identification of new therapeutic targets. LIST OF PUBLICATIONS I. Macrophages suppress T cell responses and arthritis development in mice by producing reactive oxygen species. Kyra A. Gelderman, Malin Hultqvist, Angela Pizzolla, Ming Zhao, Kutty Selva Nandakumar, Ragnar Mattsson, Rikard Holmdahl. Journal of Clinical Investigation 2007; 117(10):3020-8 II. CD68-expressing cells can prime T cells and initiate autoimmune arthritis in the absence of reactive oxygen species. Angela Pizzolla*, Kyra A. Gelderman*, Malin Hultqvist, Mikael Vestberg, Kenth Gustafsson, Ragnar Mattsson, Rikard Holmdahl. European Journal of Immunology 2011; 41(2):403-12 III. Reactive Oxygen Species produced by the NOX2 Complex in Monocytes Protect from Bacterial Infections in Mice. Angela Pizzolla, Malin Hultqvist, Bo Nilson, Melissa J. Grimm, Tove Eneljung, Ing-Marie Jonsson, Margareta Verdrengh, Tiina Kelkka, Inger Gjertsson, Brahm H. Segal, Rikard Holmdahl. Submitted IV. A new model of arthritis induced by a glucose-6-phosphate isomerase peptide: immunological requirements and peptide characterization. Angela Pizzolla, Frida Laulund and Rikard Holmdahl Manuscript * These authors contributed equally to the work" @default.
- W1755667245 created "2016-06-24" @default.
- W1755667245 creator A5061585717 @default.
- W1755667245 date "2011-11-16" @default.
- W1755667245 modified "2023-09-24" @default.
- W1755667245 title "The Role of Macrophages in Regulating Inflammation by Oxidative Burst" @default.
- W1755667245 cites W132781887 @default.
- W1755667245 cites W1490165777 @default.
- W1755667245 cites W1521993208 @default.
- W1755667245 cites W1534058357 @default.
- W1755667245 cites W1549114512 @default.
- W1755667245 cites W1571684154 @default.
- W1755667245 cites W1586192659 @default.
- W1755667245 cites W1587695215 @default.
- W1755667245 cites W1595028313 @default.
- W1755667245 cites W1597099854 @default.
- W1755667245 cites W1598564250 @default.
- W1755667245 cites W1619278260 @default.
- W1755667245 cites W1638726768 @default.
- W1755667245 cites W1716725129 @default.
- W1755667245 cites W1727958888 @default.
- W1755667245 cites W1732589186 @default.
- W1755667245 cites W1749116795 @default.
- W1755667245 cites W1826136818 @default.
- W1755667245 cites W1873874031 @default.
- W1755667245 cites W1878988841 @default.
- W1755667245 cites W1888977774 @default.
- W1755667245 cites W1911480804 @default.
- W1755667245 cites W1913625561 @default.
- W1755667245 cites W1944219509 @default.
- W1755667245 cites W1953534612 @default.
- W1755667245 cites W1953683744 @default.
- W1755667245 cites W1963791857 @default.
- W1755667245 cites W1964139565 @default.
- W1755667245 cites W1965869178 @default.
- W1755667245 cites W1968542957 @default.
- W1755667245 cites W1970935798 @default.
- W1755667245 cites W1971890827 @default.
- W1755667245 cites W1972948730 @default.
- W1755667245 cites W1974774736 @default.
- W1755667245 cites W1976912963 @default.
- W1755667245 cites W1979862705 @default.
- W1755667245 cites W1980264776 @default.
- W1755667245 cites W1980990177 @default.
- W1755667245 cites W1982709334 @default.
- W1755667245 cites W1982925959 @default.
- W1755667245 cites W1983148259 @default.
- W1755667245 cites W1984200009 @default.
- W1755667245 cites W1986006948 @default.
- W1755667245 cites W1989987141 @default.
- W1755667245 cites W1990509922 @default.
- W1755667245 cites W1991855740 @default.
- W1755667245 cites W1992145753 @default.
- W1755667245 cites W1993120305 @default.
- W1755667245 cites W1993316162 @default.
- W1755667245 cites W1993435114 @default.
- W1755667245 cites W1994402720 @default.
- W1755667245 cites W1994749115 @default.
- W1755667245 cites W1995671655 @default.
- W1755667245 cites W1996978408 @default.
- W1755667245 cites W1998098073 @default.
- W1755667245 cites W1998890104 @default.
- W1755667245 cites W2001322050 @default.
- W1755667245 cites W2003241255 @default.
- W1755667245 cites W2004286546 @default.
- W1755667245 cites W2005299533 @default.
- W1755667245 cites W2005569156 @default.
- W1755667245 cites W2008656776 @default.
- W1755667245 cites W2008716918 @default.
- W1755667245 cites W2009588836 @default.
- W1755667245 cites W2013437439 @default.
- W1755667245 cites W2013559440 @default.
- W1755667245 cites W2014081699 @default.
- W1755667245 cites W2014594279 @default.
- W1755667245 cites W2015865604 @default.
- W1755667245 cites W2016920925 @default.
- W1755667245 cites W2019570600 @default.
- W1755667245 cites W2020276399 @default.
- W1755667245 cites W2022603305 @default.
- W1755667245 cites W2022713850 @default.
- W1755667245 cites W2023691634 @default.
- W1755667245 cites W2024988150 @default.
- W1755667245 cites W2025408360 @default.
- W1755667245 cites W2025939140 @default.
- W1755667245 cites W2027179806 @default.
- W1755667245 cites W2029925670 @default.
- W1755667245 cites W2031750654 @default.
- W1755667245 cites W2035036601 @default.
- W1755667245 cites W2036312601 @default.
- W1755667245 cites W2036572485 @default.
- W1755667245 cites W2036899308 @default.
- W1755667245 cites W2037620263 @default.
- W1755667245 cites W2038344315 @default.
- W1755667245 cites W2038753879 @default.
- W1755667245 cites W2039190334 @default.
- W1755667245 cites W2040014704 @default.
- W1755667245 cites W2040937120 @default.
- W1755667245 cites W2041019072 @default.
- W1755667245 cites W2041071307 @default.
- W1755667245 cites W2041729262 @default.