The central role of dendritic cells and interferon-alpha in SLE.
OBJECTIVE
Until recently, systemic lupus erythematosus has been viewed mainly as a B-cell disease resulting from altered T cell-B cell interactions. The recognition of the fundamental role of dendritic cells in the control of tolerance and immunity led to the hypothesis that systemic lupus erythematosus may be driven through unabated dendritic cell activation. This review summarizes the recently uncovered role of dendritic cell subsets and one of their products, interferon-alpha, in the pathophysiology of systemic lupus erythematosus.


RESULTS
CD14+ monocytes isolated from the blood of patients with systemic lupus erythematosus, but not those from healthy individuals, act as dendritic cells. Their activation is driven by circulating interferon-alpha that may come from one of the dendritic cell subsets (ie, plasmacytoid dendritic cells that infiltrate systemic lupus erythematosus skin lesions). Although only a fraction of patients with active systemic lupus erythematosus show circulating interferon-alpha, blood mononuclear cells from all of them display an interferon-alpha signature.


CONCLUSIONS
The disease model that the authors propose places interferon-alpha at the center of the immunologic abnormalities observed in systemic lupus erythematosus, and poses interferon-alpha and/or interferon-alpha-producing cells as novel targets for therapy in this disease. The authors surmise that type I interferon antagonists will bring systemic lupus erythematosus patients the relief that tumor necrosis factor antagonists brought to patients with rheumatoid arthritis.
Pascual
Virginia
V
Baylor Institute for Immunology Research, Dallas, Texas 75204, USA. Virginip@Baylorhealth.edu
Banchereau
Jacques
J
Palucka
A Karolina
AK
D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D016898:Interferon-alpha