Cited by 96Rheumatoid Arthritis Research and TherapiesT-cell and B-cell ImmunologyNatural Compounds in Disease Treatment

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 C M, Hansson, Ann-Sofie, Nandakumar, Kutty S, Bäcklund, Johan, Holmdahl, Rikard·2001·The Journal of Immunology

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-γ, IL-2, and IL-4 after mitogen stimulation; however, macrophages showed a reduced TNF-α 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.

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Crossref · 10.4049/jimmunol.167.6.3505

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  • IL-10-deficient mice have increased susceptibility to both inflammatory bowel disease and adjuvant arthritis.

    “IL-10-deficient mice have increased susceptibility to both inflammatory bowel disease and adjuvant arthritis”
  • Rat strains with a diminished corticotropin-releasing factor response are prone to developing adjuvant-induced inflammatory diseases.

    “rat strains that mount a diminished corticotropin-releasing factor (a polypeptide hormone and neurotransmitter) response are prone to developing adjuvant-induced inflammatory diseases (11)(12)(13).”

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Authors
Johansson, A. C. M., Hansson, A.-S., Nandakumar, K. S., Bäcklund, J., & Holmdahl, R.
Affiliations
  • Section for Medical Inflammation Research, University of Lund , Lund ,
  • Lund University (SE)
Venue
The Journal of Immunology
Published
2001-09
Volume
167
Issue
6
Pages
3505-3512
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W2101526205
Cited by
96
References
65
Citations by year
2024: 1 · 2022: 1 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 5 · 2014: 5 · 2013: 6 · 2012: 5
FWCI
5.23
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
Keywords
IL-10, collagen-induced arthritis, anti-collagen type II antibodies, IL-10-deficient mice, T cell tolerance, rheumatoid arthritis, cytokine deficiency, immunodominant epitopes
MeSH terms
Animals, Antibodies, Monoclonal, Arthritis, Arthritis, Experimental, Autoimmune Diseases, Colitis, Disease Models, Animal, Genotype, Immune Tolerance, Immunization, Immunization, Passive, Macrophages, Male, Mice, Inbred C57BL, Mice, Transgenic, Specific Pathogen-Free Organisms, Tumor Necrosis Factor-alpha, Immunodominant Epitopes, Cytokines, Interleukin-10, Mice, Knockout, Collagen Type II, Mice

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