Inflammation in the Central Nervous System and Th17 Responses Are Inhibited by IFN-γ–Induced IL-18 Binding Protein
| Autor: | Jason M. Millward, Rachel D. Wheeler, Morten Løbner, Trevor Owens |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Central Nervous System
Male Encephalomyelitis Autoimmune Experimental medicine.medical_treatment Immunology Central nervous system Inflammation Biology Cell Line Pathogenesis Interferon-gamma Mice medicine Animals Humans Immunology and Allergy Interferon gamma Injections Spinal Mice Knockout Reverse Transcriptase Polymerase Chain Reaction Multiple sclerosis Interleukin-17 Interleukin-18 T-Lymphocytes Helper-Inducer Flow Cytometry medicine.disease Mice Inbred C57BL Cytokine medicine.anatomical_structure Intercellular Signaling Peptides and Proteins Female Interleukin 18 Interleukin 17 medicine.symptom medicine.drug |
| Zdroj: | The Journal of Immunology. 185:2458-2466 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.0902153 |
| Popis: | Inflammatory responses are essential for immune protection but may also cause pathology and must be regulated. Both Th1 and Th17 cells are implicated in the pathogenesis of autoimmune inflammatory diseases, such as multiple sclerosis. We show in this study that IL-18–binding protein (IL-18bp), the endogenous inhibitor of the Th1-promoting cytokine IL-18, is upregulated by IFN-γ in resident microglial cells in the CNS during multiple sclerosis-like disease in mice. Test of function by overexpression of IL-18bp in the CNS using a viral vector led to marked reduction in Th17 responses and robust inhibition of incidence, severity, and histopathology of disease, independently of IFN-γ. The disease-limiting action of IL-18bp included suppression of APC-derived Th17-polarizing cytokines. IL-18bp thus acts as a sensor for IFN-γ and can regulate both Th1 and Th17 responses in the CNS. |
| Databáze: | OpenAIRE |
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