IL-27 Induces a Th1 Immune Response and Susceptibility to Experimental Arthritis
| Autor: | Yanxia Cao, Paul D. Doodes, Tibor T. Glant, Alison Finnegan |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_treatment
Immunology Arthritis Spleen Inflammation Peptidoglycan Lymphocyte Activation Antibodies Interferon-gamma Mice medicine Animals Humans Immunology and Allergy Receptors Cytokine Interleukin 27 business.industry Interleukins Interleukin-17 Interleukin Receptors Interleukin Th1 Cells medicine.disease Arthritis Experimental Mice Mutant Strains medicine.anatomical_structure Cytokine Rheumatoid arthritis Experimental pathology Joints Disease Susceptibility medicine.symptom business |
| Zdroj: | The Journal of Immunology. 180:922-930 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.180.2.922 |
| Popis: | IL-27 is the newest member of the cytokine family comprised of IL-12 and IL-23. IL-27 was originally described as a cytokine that along with IL-12 induces the differentiation of naive precursor T cells into Th1 effector cells. This activity has been called into question based on evidence in infectious disease and autoimmune models in which IL-27 is not absolutely required for the generation of IFN-γ, and IL-27 plays a regulatory role in controlling inflammation. We have previously reported in proteoglycan-induced arthritis (PGIA), a model of rheumatoid arthritis, that severe arthritis is dependent on the production of IFN-γ. In this study, we report that IL-27 was expressed in spleen and joint tissues of arthritic mice. We determined the involvement of IL-27 in PGIA by assessing the progression of arthritis in IL-27R−/− mice. Development of arthritis in IL-27R−/− mice was delayed and severity reduced in comparison with IL-27R+/+ littermate controls. Histology confirmed a reduction in joint cellularity, cartilage destruction, and bone erosion. Diminished arthritis was associated with fewer T cells producing IFN-γ and decreased IFN-γ secretion overtime. Moreover, the frequency of IL-4- and IL-17-expressing T cells and the production of IL-4 and IL-17 were similar in IL-27R−/− mice and controls. Our results indicate that IL-27 is critically involved in the induction of inflammation in PGIA. IL-27 functions by inducing the differentiation of IFN-γ-producing T cells in vivo that are essential for the development of arthritis. |
| Databáze: | OpenAIRE |
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