Leech, M. D., Barr, T., Turner, D.G., Brown, S., O'Connor, R.A., Gray, D., Mellanby, R.J. and Anderton, S.M. (2013) Cutting edge: IL-6-dependent autoimmune disease: dendritic cells as a sufficient, but transient, source. Journal of Immunology, 190(3), pp. 881-885. (doi: 10.4049/jimmunol.1202925)
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Abstract
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.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Barr, Dr Tom |
Authors: | Leech, M. D., Barr, T., Turner, D.G., Brown, S., O'Connor, R.A., Gray, D., Mellanby, R.J., and Anderton, S.M. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Journal of Immunology |
Publisher: | American Association of Immunologists |
ISSN: | 0022-1767 |
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