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Toll-like receptor 9-dependent and -independent dendritic cell activation by chromatin-immunoglobulin G complexes

Abstract

Dendritic cell (DC) activation by nucleic acid-containing immunoglobulin (Ig)G complexes has been implicated in systemic lupus erythematosus (SLE) pathogenesis. However, the mechanisms responsible for activation and subsequent disease induction are not completely understood. Here we show that murine DCs are much more effectively activated by immune complexes that contain IgG bound to chromatin than by immune complexes that contain foreign protein. Activation by these chromatin immune complexes occurs by two distinct pathways. One pathway involves dual engagement of the Fc receptor FcgammaRIII and Toll-like receptor (TLR)9, whereas the other is TLR9 independent. Furthermore, there is a characteristic cytokine profile elicited by the chromatin immune complexes that distinguishes this response from that of conventional TLR ligands, notably the induction of BAFF and the lack of induction of interleukin 12. The data establish a critical role for self-antigen in DC activation and explain how the innate immune system might drive the adaptive immune response in SLE.

Type Journal
ISBN 0022-1007 (Print)
Authors Boule, M. W.;Broughton, C.;Mackay, F.;Akira, S.;Marshak-Rothstein, A.;Rifkin, I. R. :
Publisher Name JOURNAL OF EXPERIMENTAL MEDICINE
Published Date 2004-01-01
Published Volume 199
Published Issue 12
Published Pages 1631-40
Status Published in-print
URL link to publisher's version http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15197227
OpenAccess link to author's accepted manuscript version https://publications.gimr.garvan.org.au/open-access/1756