Cutting Edge: IL-6-Dependent Autoimmune Disease: Dendritic Cells as a Sufficient, but Transient, Source

Melanie D Leech, Tom A Barr, Darryl G Turner, Sheila Brown, Richard A O'Connor, David Gray, Richard J Mellanby, Stephen M Anderton

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)881-885
Number of pages5
JournalJournal of Immunology
Volume190
Issue number3
DOIs
Publication statusPublished - 1 Feb 2013

Fingerprint

Dive into the research topics of 'Cutting Edge: IL-6-Dependent Autoimmune Disease: Dendritic Cells as a Sufficient, but Transient, Source'. Together they form a unique fingerprint.

Cite this