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Chronic active arthritis driven by macrophages without involvement of T cells : A Novel Experimental Model of Rheumatoid Arthritis

Hagert, Cecilia ; Sareila, Outi ; Kelkka, Tiina ; Nandakumar, Kutty Selva ; Collin, Mattias LU orcid ; Xu, Bingze ; Guérard, Simon ; Bäcklund, Johan LU ; Jalkanen, Sirpa and Holmdahl, Rikard LU (2018) In Arthritis & Rheumatology 70(8).
Abstract
OBJECTIVE: To develop a new chronic RA model which is driven by the innate immune system.METHOD: The injection of a cocktail of four monoclonal antibodies against collagen type II followed by intra-peritoneal injections of mannan (from Saccharomyces cerevisiae) on days 5 and 60 led to the development of chronic arthritis in B10.Q mice. The role of the innate versus the adaptive immune system in this arthritis model was investigated using genetically modified mouse strains.RESULT: A new model of chronic relapsing arthritis was characterized and found to lead to a persistent, chronic arthritis. This relapsing disease was driven by macrophages lacking the ability to make a reactive oxygen species (ROS) response and was associated with the... (More)
OBJECTIVE: To develop a new chronic RA model which is driven by the innate immune system.METHOD: The injection of a cocktail of four monoclonal antibodies against collagen type II followed by intra-peritoneal injections of mannan (from Saccharomyces cerevisiae) on days 5 and 60 led to the development of chronic arthritis in B10.Q mice. The role of the innate versus the adaptive immune system in this arthritis model was investigated using genetically modified mouse strains.RESULT: A new model of chronic relapsing arthritis was characterized and found to lead to a persistent, chronic arthritis. This relapsing disease was driven by macrophages lacking the ability to make a reactive oxygen species (ROS) response and was associated with the classical/alternative, but not the lectin complement pathway. The disease was also independent of FcγRIII as well as adaptive immune cells, B and T cells, indicating the innate immune system, involving complement activation, as the sole driver of chronicity.CONCLUSION: Chronic active arthritis can be driven by macrophages without the involvement of T and B cells in the adaptive immune system. This article is protected by copyright. All rights reserved. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Journal Article
in
Arthritis & Rheumatology
volume
70
issue
8
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:29513929
  • scopus:85050645467
ISSN
1529-0131
DOI
10.1002/art.40482
language
English
LU publication?
yes
id
5ef0c489-9245-4325-999b-21391f490c34
date added to LUP
2018-03-09 16:21:05
date last changed
2024-04-01 02:31:31
@article{5ef0c489-9245-4325-999b-21391f490c34,
  abstract     = {{OBJECTIVE: To develop a new chronic RA model which is driven by the innate immune system.METHOD: The injection of a cocktail of four monoclonal antibodies against collagen type II followed by intra-peritoneal injections of mannan (from Saccharomyces cerevisiae) on days 5 and 60 led to the development of chronic arthritis in B10.Q mice. The role of the innate versus the adaptive immune system in this arthritis model was investigated using genetically modified mouse strains.RESULT: A new model of chronic relapsing arthritis was characterized and found to lead to a persistent, chronic arthritis. This relapsing disease was driven by macrophages lacking the ability to make a reactive oxygen species (ROS) response and was associated with the classical/alternative, but not the lectin complement pathway. The disease was also independent of FcγRIII as well as adaptive immune cells, B and T cells, indicating the innate immune system, involving complement activation, as the sole driver of chronicity.CONCLUSION: Chronic active arthritis can be driven by macrophages without the involvement of T and B cells in the adaptive immune system. This article is protected by copyright. All rights reserved.}},
  author       = {{Hagert, Cecilia and Sareila, Outi and Kelkka, Tiina and Nandakumar, Kutty Selva and Collin, Mattias and Xu, Bingze and Guérard, Simon and Bäcklund, Johan and Jalkanen, Sirpa and Holmdahl, Rikard}},
  issn         = {{1529-0131}},
  keywords     = {{Journal Article}},
  language     = {{eng}},
  number       = {{8}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Arthritis & Rheumatology}},
  title        = {{Chronic active arthritis driven by macrophages without involvement of T cells : A Novel Experimental Model of Rheumatoid Arthritis}},
  url          = {{http://dx.doi.org/10.1002/art.40482}},
  doi          = {{10.1002/art.40482}},
  volume       = {{70}},
  year         = {{2018}},
}