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

Pizzolla, Angela; Gelderman, Kyra; Hultqvist, Malin LU ; Vestberg, Mikael; Gustafsson, Kenth; Mattsson, Ragnar LU and Holmdahl, Rikard LU (2011) In European Journal of Immunology 41(2). p.403-412
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Immunology
volume
41
issue
2
pages
403 - 412
publisher
John Wiley & Sons
external identifiers
  • wos:000287159600017
  • pmid:21268010
  • scopus:78851469358
ISSN
1521-4141
DOI
10.1002/eji.201040598
language
English
LU publication?
yes
id
e1443b19-a719-4614-b968-674ba56427dc (old id 1777062)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21268010?dopt=Abstract
date added to LUP
2011-02-01 09:44:43
date last changed
2017-10-29 04:28:28
@article{e1443b19-a719-4614-b968-674ba56427dc,
  abstract     = {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.},
  author       = {Pizzolla, Angela and Gelderman, Kyra and Hultqvist, Malin and Vestberg, Mikael and Gustafsson, Kenth and Mattsson, Ragnar and Holmdahl, Rikard},
  issn         = {1521-4141},
  language     = {eng},
  number       = {2},
  pages        = {403--412},
  publisher    = {John Wiley & Sons},
  series       = {European Journal of Immunology},
  title        = {CD68-expressing cells can prime T cells and initiate autoimmune arthritis in the absence of reactive oxygen species.},
  url          = {http://dx.doi.org/10.1002/eji.201040598},
  volume       = {41},
  year         = {2011},
}