Cutting edge: IL-6-dependent autoimmune disease: dendritic cells as a sufficient, but transient, source

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)

Full text not currently available from Enlighten.

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
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 > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Immunology
Publisher:American Association of Immunologists
ISSN:0022-1767

University Staff: Request a correction | Enlighten Editors: Update this record