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Suppression of ongoing adjuvant-induced arthritis by neutralizing the function of the p28 subunit of IL-27
- Source :
- Journal of immunology (Baltimore, Md. : 1950). 173(2)
- Publication Year :
- 2004
-
Abstract
- IL-27 is a recently defined family member of the long-chain four-helix bundle cytokines, which consists of EBI3, an IL-12p40-related protein, and p28, an IL-12p35-related polypeptide. The role of IL-27 in the regulation of inflammatory autoimmune diseases has never been studied. The current study uses the DNA vaccination technology, and highly specific Abs to the p28 subunit of IL-27 that were generated by this technology, to delineate its role in the regulation of adjuvant-induced arthritis in Lewis rats. Neutralizing the in vivo function of IL-27 by targeted DNA vaccines and by Abs against IL-27 p28 that were produced in protected donors could rapidly suppress an ongoing disease. Disease suppression was associated with a reduced ex vivo production of inflammatory cytokines. We then used these Abs to investigate the mechanistic basis of disease suppression, showing that IL-27 is not only involved in directing the polarization of naive T cells, but also affects the proliferative response and cytokine production of Ag-specific effector/memory Th1 cells. This may explain, in part, its important role in the regulation of inflammatory autoimmune diseases, and also suggest novel ways of therapy.
- Subjects :
- Effector
medicine.medical_treatment
Interleukins
T-Lymphocytes
Immunology
Arthritis
EBI3
Biology
medicine.disease
Arthritis, Experimental
Proinflammatory cytokine
DNA vaccination
Rats
Cytokine
In vivo
medicine
Vaccines, DNA
Immunology and Allergy
Animals
Cytokines
Female
Ex vivo
Autoantibodies
Plasmids
Subjects
Details
- ISSN :
- 00221767
- Volume :
- 173
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....2689c6bbff8e555d6785e1f379253e8b