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Science 16 November 2001:
Vol. 294. no. 5546, pp. 1540 - 1543
DOI: 10.1126/science.1064890
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Reports

Induction of Dendritic Cell Differentiation by IFN-alpha in Systemic Lupus Erythematosus

Patrick Blanco,1* A. Karolina Palucka,1* Michelle Gill,12 Virginia Pascual,12 Jacques Banchereau1dagger

Dendritic cells (DCs) are important in regulating both immunity and tolerance. Hence, we hypothesized that systemic lupus erythematosus (SLE), an autoimmune disease characterized by autoreactive B and T cells, may be caused by alterations in the functions of DCs. Consistent with this, monocytes from SLE patients' blood were found to function as antigen-presenting cells, in vitro. Furthermore, serum from SLE patients induced normal monocytes to differentiate into DCs. These DCs could capture antigens from dying cells and present them to CD4-positive T cells. The capacity of SLE patients' serum to induce DC differentiation correlated with disease activity and depended on the actions of interferon-alpha (IFN-alpha ). Thus, unabated induction of DCs by IFN-alpha may drive the autoimmune response in SLE.

1 Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
2 The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: j.banchereau{at}baylordallas.edu

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A. J. Cappione, A. E. Pugh-Bernard, J. H. Anolik, and I. Sanz (2004)
J. Immunol. 172, 4298-4307
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The genetic basis of systemic lupus erythematosus--knowledge of today and thoughts for tomorrow.
L. Prokunina and M. Alarcon-Riquelme (2004)
Hum. Mol. Genet. 13, R143-148
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Thrombopoietin cooperates with FLT3-ligand in the generation of plasmacytoid dendritic cell precursors from human hematopoietic progenitors.
W. Chen, S. Antonenko, J. M. Sederstrom, X. Liang, A. S. H. Chan, H. Kanzler, B. Blom, B. R. Blazar, and Y.-J. Liu (2004)
Blood 103, 2547-2553
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Cell surface expression of an endoplasmic reticulum resident heat shock protein gp96 triggers MyD88-dependent systemic autoimmune diseases.
B. Liu, J. Dai, H. Zheng, D. Stoilova, S. Sun, and Z. Li (2003)
PNAS 1