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Scientists find a key element of lupus, suggesting better drug targets
Date:2/4/2013

ound evidence that a powerful class of immune-stimulating chemicals, known as type I interferons, are essential to the vicious cycle of lupus autoimmunity.

The cycle apparently begins when certain immune cells mistakenly detect self-proteins and nucleic acids as "foreign" and begin pumping out type I interferons. This mobilizes other elements of the immune system, including the antibody response, and soon autoantibodies are attacking self-molecules in healthy cells. The autoantibodies in turn present these "foreign" molecules to type I interferon-producing cells, adding fuel to the autoimmune fire.

Lab-dish evidence has suggested that the key producers of type I interferons in lupus are a relatively sparse class of immune cells known as plasmacytoid dendritic cells (pDCs). In the new study, Theofilopoulos and his colleagues sought more conclusive evidence of pDCs' role, using mouse models of lupus.

In Search of Evidence

The experiments were led by first author Roberto Baccala, an associate professor in the TSRI Department of Immunology and Microbial Science who has worked with Theofilopoulos on lupus-related research for the past two decades. To help determine whether lupus can develop in the absence of pDCs, the TSRI scientists collaborated with Keiko Ozato, an expert on immune cell genetics at the National Institutes of Health. Ozato has developed a strain of mice that have no pDCs due to lack of a key gene (IRF8) needed for these cells' development.

The team knocked out this gene in another strain of mice that normally succumbs to a lupus-like autoimmune disease with age. These mice grew up without pDCs and, as a result, were largely protected from the disease.

"When we injected a standard inducer of interferons into these mice, they didn't produce detectable interferons," said Baccala. "And when we watched the animals for the usual development of lupus, we found that autoantibodies were practically
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert  

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