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

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2012 Dec 26

PMID 23267024

Citations 24

Authors

Melanie D Leech

Tom A Barr

Darryl G Turner

Sheila Brown

Richard A OConnor

David Gray

Richard J Mellanby

Stephen M Anderton

Affiliations

Soon will be listed here.

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.

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