Three Toll-Like Receptors Implicated in Lupus

Researchers have shown that three particular Toll-like receptors (TLRs) may play a key role in the development of systemic lupus erythematosus (SLE or lupus), an autoimmune disease affecting over 1.5 million Americans. In mouse strains that spontaneously develop human-similar forms of SLE, the authors showed that TRL 3, TRL 7, and TRL 9 appear to be required for the full autoimmune response to take place. These TLRs may thus provide effective targets for the development of new treatments for lupus, as well as other autoimmune diseases. The researchers did their experiments by first engineering lupus-prone mice to have a non-functioning form of the gene (Unc93b1) that is required for transport of the three TRLs from where they are made to the cell’s endolysosome where they do their work. In the endolysosome, TLRs normally detect foreign DNA and RNA and instruct the body’s immune system to make antibodies against these materials. But the production of antibodies against foreign DNA and RNA seems to be particularly prone to error. The most common types of autoantibodies found in lupus patients are ones to the body's own genetic material—the DNA and RNA that resides inside the cell's nucleus. As a result, doctors often test for the presence of "antinuclear" antibodies to diagnose lupus. In their study, the researchers found that compared to the lupus-prone mice with a functioning Unc93b1 gene, the lupus-prone mice with the Unc93b1 mutation produced fewer antinuclear antibodies and had fewer and less severe symptoms of lupus. "It seems like these three TLRs are absolutely required for optimal autoantibody production," said Dr. Dwight Kono, an author of the study.
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