The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

CD68-expressing cells can prime T cells and initiate autoimmune arthritis in the absence of reactive oxygen species.

På svenska

Author

  • Angela Pizzolla
  • Kyra Gelderman
  • Malin Hultqvist
  • Mikael Vestberg
  • Kenth Gustafsson
  • Ragnar Mattsson
  • Rikard Holmdahl

Summary, in English

It is widely believed that DC, but not macrophages, prime naïve T cells in vivo. Here, we investigated the ability of CD68-expressing cells (commonly defined as macrophages) in priming autoreactive T cells and initiating collagen-induced arthritis (CIA) in the mouse. For this purpose, a transgenic mouse was developed (MBQ mouse) where macrophages exclusively expressed the MHC class II H2-A(q) (A(q) ) on an H2-A(p) (A(p) ) background. A(q) , but not A(p) expression mediates susceptibility to CIA through presentation of type II collagen (CII) to T cells. CIA severity is enhanced by a mutation in the Ncf1 gene, impairing reactive oxygen species (ROS) production by the phagocyte NADPH oxidase (NOX2) complex. Expression of functional Ncf1 on macrophages was previously shown to protect from severe CIA. To study the effect of ROS on macrophage-mediated priming of T cells, the Ncf1 mutation was introduced in the MBQ mouse. Upon CII immunization, Ncf1-mutated MBQ mice, but not Ncf1 wild-type MBQ mice nor Ncf1-mutated A(p) mice, activated autoreactive T cells and developed CIA. These findings demonstrate for the first time that macrophages can initiate arthritis and that the process is negatively regulated by ROS produced via the NOX2 complex.

Department/s

  • Immunology

Publishing year

2011

Language

English

Pages

403-412

Publication/Series

European Journal of Immunology

Volume

41

Issue

2

Document type

Journal article

Publisher

John Wiley & Sons Inc.

Topic

  • Immunology in the medical area

Status

Published

Research group

  • Immunology

ISBN/ISSN/Other

  • ISSN: 1521-4141