Serum from a lupus patient turns monocytes into dendritic cells.

Banchereau/AAAS

The cellular defect that underlies the autoimmune disease lupus may finally have been uncovered. Overactive dendritic cells may be inciting attacks on the patient's own tissues.In lupus, the immune system batters the skin, kidneys, brain, and other organs, but the stimulus for the attack has eluded explanation. Jacques Banchereau (Baylor Institute for Immunology Research, Dallas, TX) and colleagues found that serum from lupus patients spurs monocytes to mature into dendritic cells that may trigger an autoimmune reaction. The dendritic cells gobbled up fragments of dead body cells and presented them to autologous CD4 T cells.

What stimulates the maturation of monocytes? The research implicated α interferon, which is produced by one class of dendritic cells and is elevated in people with lupus. According to Banchereau, the results suggest that hyperactive dendritic cells, driven by high levels of α interferon, may cause lupus.

That still leaves a puzzle, however. How to explain the high levels of interferon, especially when the interferon-producing dendritic cells are often scarce in the blood of lupus patients? Banchereau thinks that armies of dendritic cells have deployed from the blood into the tissues. There, if they are simulated by a virus, the errant cells may start pumping out α interferon, leading to the self-destructive attacks that produce symptoms like vasculitis and rashes.

Patients could soon benefit from this work, Banchereau predicts. Steroids and immunosuppressants can ease symptoms of lupus, but they cannot cure the disease. “This provides us with a target for therapeutic intervention,” he says. ▪

Reference:

Blanco, P., et al.
2001
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