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IL-10-deficient B10.Q mice develop more severe collagen-induced arthritis, but are protected from arthritis induced with anti-type II collagen antibodies

Johansson, Åsa LU ; Liedberg, Ann-Sofie LU ; Kutty Selva, Nandakumar LU ; Bäcklund, Johan LU and Holmdahl, Rikard LU (2001) In Journal of Immunology 167(6). p.3505-3512
Abstract
IL-10 is a pleiotropic cytokine with stimulatory and inhibitory properties, and is thought to have a protective role in rheumatoid arthritis and collagen-induced arthritis (CIA). In this study, we investigated how IL-10 deficiency affects CIA and anti-collagen type II (CII) Ab-transferred arthritis in C57BL/10.Q (B10.Q) mice. The B10.Q.IL-10(-/-) mice had an 8-cM 129/Ola fragment around the IL-10 gene. The mice were treated with antibiotics, appeared healthy, and had no colitis. T cells from IL-10(-/-) mice expressed similar levels of IFN-gamma, IL-2, and IL-4 after mitogen stimulation; however, macrophages showed a reduced TNF-alpha production compared with IL-10(+/-) littermates. IL-10(-/-) mice had an increased incidence, and a more... (More)
IL-10 is a pleiotropic cytokine with stimulatory and inhibitory properties, and is thought to have a protective role in rheumatoid arthritis and collagen-induced arthritis (CIA). In this study, we investigated how IL-10 deficiency affects CIA and anti-collagen type II (CII) Ab-transferred arthritis in C57BL/10.Q (B10.Q) mice. The B10.Q.IL-10(-/-) mice had an 8-cM 129/Ola fragment around the IL-10 gene. The mice were treated with antibiotics, appeared healthy, and had no colitis. T cells from IL-10(-/-) mice expressed similar levels of IFN-gamma, IL-2, and IL-4 after mitogen stimulation; however, macrophages showed a reduced TNF-alpha production compared with IL-10(+/-) littermates. IL-10(-/-) mice had an increased incidence, and a more severe CIA disease than the IL-10+/- littermates. To study the role of IL-10 in T cell tolerance, IL-10(-/-) were crossed into mice carrying the immunodominant epitope, CII(256-270), in cartilage (MMC) or in skin (TSC). Both IL-10(-/-) and IL-10(+/-) MMC and TSC mice were completely tolerized against CIA, indicating that lack of IL-10 in this context did not break tolerance. To investigate whether IL-10 was important in the effector phase of CIA, arthritis was induced with anti-CII Abs. Surprisingly, IL-10(-/-) were less susceptible to Ab-transferred arthritis, as only 30% showed signs of disease compared with 90% of the littermates. Therefore, IL-10 seemed to have a protective role in CIA, but seemed to exacerbate the arthritogenicity of anti-CII Abs. These data emphasize the importance of studying IL-10 in a defined genetic context in vivo, to understand its role in a complex disease like arthritis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
167
issue
6
pages
3505 - 3512
publisher
American Association of Immunologists
external identifiers
  • wos:000172392000061
  • scopus:0035884447
ISSN
1550-6606
language
English
LU publication?
yes
id
7cb477e8-8d5f-464a-a6c5-6df51a6c65da (old id 1118651)
date added to LUP
2008-07-01 08:58:54
date last changed
2018-03-18 04:34:24
@article{7cb477e8-8d5f-464a-a6c5-6df51a6c65da,
  abstract     = {IL-10 is a pleiotropic cytokine with stimulatory and inhibitory properties, and is thought to have a protective role in rheumatoid arthritis and collagen-induced arthritis (CIA). In this study, we investigated how IL-10 deficiency affects CIA and anti-collagen type II (CII) Ab-transferred arthritis in C57BL/10.Q (B10.Q) mice. The B10.Q.IL-10(-/-) mice had an 8-cM 129/Ola fragment around the IL-10 gene. The mice were treated with antibiotics, appeared healthy, and had no colitis. T cells from IL-10(-/-) mice expressed similar levels of IFN-gamma, IL-2, and IL-4 after mitogen stimulation; however, macrophages showed a reduced TNF-alpha production compared with IL-10(+/-) littermates. IL-10(-/-) mice had an increased incidence, and a more severe CIA disease than the IL-10+/- littermates. To study the role of IL-10 in T cell tolerance, IL-10(-/-) were crossed into mice carrying the immunodominant epitope, CII(256-270), in cartilage (MMC) or in skin (TSC). Both IL-10(-/-) and IL-10(+/-) MMC and TSC mice were completely tolerized against CIA, indicating that lack of IL-10 in this context did not break tolerance. To investigate whether IL-10 was important in the effector phase of CIA, arthritis was induced with anti-CII Abs. Surprisingly, IL-10(-/-) were less susceptible to Ab-transferred arthritis, as only 30% showed signs of disease compared with 90% of the littermates. Therefore, IL-10 seemed to have a protective role in CIA, but seemed to exacerbate the arthritogenicity of anti-CII Abs. These data emphasize the importance of studying IL-10 in a defined genetic context in vivo, to understand its role in a complex disease like arthritis.},
  author       = {Johansson, Åsa and Liedberg, Ann-Sofie and Kutty Selva, Nandakumar and Bäcklund, Johan and Holmdahl, Rikard},
  issn         = {1550-6606},
  language     = {eng},
  number       = {6},
  pages        = {3505--3512},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {IL-10-deficient B10.Q mice develop more severe collagen-induced arthritis, but are protected from arthritis induced with anti-type II collagen antibodies},
  volume       = {167},
  year         = {2001},
}