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Arthritis Res Ther. 2006; 8(2): R49.
Published online Feb 28, 2006. doi:  10.1186/ar1911
PMCID: PMC1526610
Abnormal costimulatory phenotype and function of dendritic cells before and after the onset of severe murine lupus
Lucrezia Colonna,1 Joudy-Ann Dinnall,1 Debra K Shivers,1 Lorenza Frisoni,2 Roberto Caricchio,2 and Stefania Galluccicorresponding author1
1Laboratory of Dendritic Cell Biology, Division of Rheumatology, Joseph Stokes' Jr. Research Institute, Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA 19104-4318, USA
2Division of Rheumatology, School of Medicine, University of Pennsylvania, 751 BRB II/III, 421 Curie Blvd, Philadelphia, PA 19104, USA
corresponding authorCorresponding author.
Lucrezia Colonna: lc2238/at/columbia.edu; Joudy-Ann Dinnall: dinnall/at/email.chop.edu; Debra K Shivers: shivers/at/email.chop.edu; Lorenza Frisoni: lorenzaf/at/mail.med.upenn.edu; Roberto Caricchio: rocarri2/at/mail.med.upenn.edu; Stefania Gallucci: gallucci/at/email.chop.edu
Received December 12, 2005; Revisions requested January 10, 2006; Revised January 31, 2006; Accepted February 2, 2006.
Abstract
We analyzed the activation and function of dendritic cells (DCs) in the spleens of diseased, lupus-prone NZM2410 and NZB-W/F1 mice and age-matched BALB/c and C57BL/6 control mice. Lupus DCs showed an altered ex vivo costimulatory profile, with a significant increase in the expression of CD40, decreased expression of CD80 and CD54, and normal expression of CD86. DCs from young lupus-prone NZM2410 mice, before the development of the disease, expressed normal levels of CD80 and CD86 but already overexpressed CD40. The increase in CD40-positive cells was specific for DCs and involved the subset of myeloid and CD8α+ DCs before disease onset, with a small involvement of plasmacytoid DCs in diseased mice. In vitro data from bone marrow-derived DCs and splenic myeloid DCs suggest that the overexpression of CD40 is not due to a primary alteration of CD40 regulation in DCs but rather to an extrinsic stimulus. Our analyses suggest that the defect of CD80 in NZM2410 and NZB-W/F1 mice, which closely resembles the costimulatory defect found in DCs from humans with systemic lupus erythematosus, is linked to the autoimmune disease. The increase in CD40 may instead participate in disease pathogenesis, being present months before any sign of autoimmunity, and its downregulation should be explored as an alternative to treatment with anti-CD40 ligand in lupus.
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