A pivotal role for the natural interferon alpha-producing cells (plasmacytoid dendritic cells) in the pathogenesis of lupus - PubMed (original) (raw)

Review

A pivotal role for the natural interferon alpha-producing cells (plasmacytoid dendritic cells) in the pathogenesis of lupus

L Rönnblom et al. J Exp Med. 2001.

No abstract available

Figures

Figure 1.

Hypothetical role of NIPCs, also termed PDCs, in SLE. The NIPCs/PDCs become activated naturally by infectious microorganisms, but in SLE also by DNA or RNA molecules in complex with autoantibodies (endogenous IFN-α inducers) in an FcγRII-dependent manner. Such nucleic acids, possibly bound to proteins, may be derived from apoptotic cells. The TLR9 is expressed on the NIPCs/PDCs and mediates responses to unmethylated CpG-DNA. The CD40 on NIPCs/PDCs deliver costimulatory signals when interacting with CD40-ligands, resulting in IL-12 production and enhanced IFN-α synthesis in response to at least CpG-DNA. The C-type lectin BDCA-2 is also depicted (natural ligand unknown) and ligation of such molecules inhibits the IFN-α production. The IFN-α finally acts on many cells, one immediate effect being costimulation (priming) of NIPCs/PDCs that is essential for efficient IFN-α production. Furthermore, the IFN-α acts on DCs and T- and B lymphocytes to counteract self-tolerance and promote autoimmunity. This results in the immune-mediated inflammation seen in SLE, as well as generation of more endogenous IFN-α inducers.

Comment on

BDCA-2, a novel plasmacytoid dendritic cell-specific type II C-type lectin, mediates antigen capture and is a potent inhibitor of interferon alpha/beta induction.
Dzionek A, Sohma Y, Nagafune J, Cella M, Colonna M, Facchetti F, Günther G, Johnston I, Lanzavecchia A, Nagasaka T, Okada T, Vermi W, Winkels G, Yamamoto T, Zysk M, Yamaguchi Y, Schmitz J. Dzionek A, et al. J Exp Med. 2001 Dec 17;194(12):1823-34. doi: 10.1084/jem.194.12.1823. J Exp Med. 2001. PMID: 11748283 Free PMC article.

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References

1. Bogdan, C. 2000. The function of type I interferons in antimicrobial immunity. Curr. Opin. Immunol. 12:419–424. - PubMed
1. Akbar, A.N., J.M. Lord, and M. Salmon. 2000. IFN-α and IFN-β: a link between immune memory and chronic inflammation. Immunol. Today. 21:337–342. - PubMed
1. Sinigaglia, F., D. D'Ambrosio, P. Panina-Bordignon, and L. Rogge. 1999. Regulation of the IL-12/IL-12R axis: a critical step in T-helper cell differentiation and effector function. Immunol. Rev. 170:65–72. - PubMed
1. Santini, S.M., C. Lapenta, M. Logozzi, S. Parlato, M. Spada, T. Di Pucchio, and F. Belardelli. 2000. Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice. J. Exp. Med. 191:1777–1788. - PMC - PubMed
1. Ruuth, K., L. Carlsson, B. Hallberg, and E. Lundgren. 2001. Interferon-α promotes survival of human primary B-lymphocytes via phosphatidylinositol 3-kinase. Biochem. Biophys. Res. Commun. 284:583–586. - PubMed

A pivotal role for the natural interferon alpha-producing cells (plasmacytoid dendritic cells) in the pathogenesis of lupus - PubMed (original) (raw)