Blockade of TLR9 agonist-induced type I interferons promotes inflammatory cytokine IFN-γ and IL-17 secretion by activated human PBMC
| Autor: | Jean Maguire van Seventer, John A. Meyers, Calvin F. Roff, Alyson J. Mangini, David Sehy, Taro Nagai, Gijs A. van Seventer |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Multiple Sclerosis
medicine.medical_treatment CD40 Ligand Immunology Lymphocyte Activation Autoantigens Biochemistry Superantigen Interleukin 23 medicine Humans Lupus Erythematosus Systemic Immunology and Allergy Antigen-presenting cell Molecular Biology Cells Cultured Antigen Presentation Superantigens CD40 biology Chemistry Models Immunological hemic and immune systems Dendritic Cells T-Lymphocytes Helper-Inducer Hematology Cytokine Oligodeoxyribonucleotides Toll-Like Receptor 9 biology.protein Interleukin 12 Cytokines CpG Islands Cytokine secretion Interleukin 17 |
| Zdroj: | Cytokine. 35:235-246 |
| ISSN: | 1043-4666 |
| DOI: | 10.1016/j.cyto.2006.09.001 |
| Popis: | Type I interferons (IFN) (IFN-alpha/beta) are recognized as both inhibitors and effectors of autoimmune disease. In multiple sclerosis, IFN-beta therapy appears beneficial, in part, due to its suppression of autoimmune inflammatory Th cell responses. In contrast, in systemic lupus erythematosus (SLE) triggering of plasmacytoid DC (pDC) Toll-like receptors (TLRs) by autoimmune complexes (autoICs) results in circulating type I IFN that appear to promote disease by driving autoantigen presentation and autoantibody production. To investigate how pDC-derived type I IFN might regulate Th cells in SLE, we examined a model in which sustained pDC stimulation by autoICs is mimicked by pretreating normal human PBMC with TLR9 agonist, CpG-A. Subsequently, PBMC Th cells are activated with superantigen, and APC are activated with CD40L. The role of CpG-A/TLR9-induced type I IFN in regulating PBMC is determined by blocking with virus-derived soluble type I IFN receptor, B18R. In summary, pretreatment with either rhIFN-alpha/beta or CpG-A inhibits PBMC secretion of superantigen-induced IFN-gamma and IL-17, and CD40L-induced IL-12p70 and IL-23. B18R prevents these effects. Data indicate that CpG-A-induced type I IFN inhibit IL-12p70-dependent PBMC IFN-gamma secretion by enhancing IL-10. Our results suggest that in SLE, circulating type I IFN may potentially act to inhibit inflammatory cytokine secretion. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect