IL-10-Deficient B10.Q Mice Develop More Severe Collagen-Induced Arthritis, but Are Protected from Arthritis Induced with Anti-Type II Collagen Antibodies
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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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”
From Physiology and immunology of the cholinergic antiinflammatory pathway (2007) · cites this paper as [12]
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).”
From Physiology and immunology of the cholinergic antiinflammatory pathway (2007) · cites this paper as [12]
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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
- Publisher
- Oxford University Press (OUP)
- 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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