Cutting edge: IL-6-dependent autoimmune disease: dendritic cells as a sufficient, but transient, source
| Autor: | Tom A. Barr, Darryl G. Turner, Stephen M. Anderton, David Gray, Sheila Brown, Richard A. O’Connor, Richard J. Mellanby, Melanie D. Leech |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
CD4-Positive T-Lymphocytes
Adoptive cell transfer Encephalomyelitis Autoimmune Experimental T cell Immunology Priming (immunology) T-Cell Antigen Receptor Specificity Biology Lymphocyte Activation Autoantigens Article Mice medicine Immunology and Allergy Animals IL-2 receptor Crosses Genetic Medicine(all) Autoimmune disease Mice Knockout Lymphokines Interleukin-6 Experimental autoimmune encephalomyelitis Lymphokine Histocompatibility Antigens Class II Immunization Passive Myelin Basic Protein Dendritic cell Dendritic Cells medicine.disease Adoptive Transfer Receptors Interleukin-6 Peptide Fragments Specific Pathogen-Free Organisms Mice Inbred C57BL medicine.anatomical_structure Myelin-Oligodendrocyte Glycoprotein |
| Zdroj: | Leech, M D, Barr, T A, Turner, D G, Brown, S, O'Connor, R A, Gray, D, Mellanby, R J & Anderton, S M 2013, ' Cutting Edge : IL-6-Dependent Autoimmune Disease: Dendritic Cells as a Sufficient, but Transient, Source ', Journal of Immunology, vol. 190, no. 3, pp. 881-885 . https://doi.org/10.4049/jimmunol.1202925 |
| ISSN: | 1550-6606 |
| DOI: | 10.4049/jimmunol.1202925 |
| Popis: | Mice lacking IL-6 are resistant to autoimmune diseases, such as experimental autoimmune encephalomyelitis (EAE), which is driven by CNS-reactive CD4+ T cells. There are multiple cellular sources of IL-6, but the critical source in EAE has been uncertain. Using cell-specific IL-6 deficiency in models of EAE induced by active immunization, passive transfer, T cell transfer, and dendritic cell transfer, we show that neither the pathogenic T cells nor CNS-resident cells are required to produce IL-6. Instead, the requirement for IL-6 was restricted to the early stages of T cell activation and was entirely controlled by dendritic cell–derived IL-6. This reflected the loss of IL-6R expression by T cells over time. These data explain why blockade of IL-6R only achieves protection against EAE if used at the time of T cell priming. The implications for therapeutic manipulation of IL-6 signaling in human T cell–driven autoimmune conditions are considered. |
| Databáze: | OpenAIRE |
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