Lupus erythematosus (or lupus), is a chronic inflammatory disease that can affect different body parts, including joints, skin, kidneys, blood cells, heart, and lungs. Now, Scripps Research Institute researchers have identified three new proteins that play a role in the development of lupus.
Lupus is one of several autoimmune diseases in which the immune system turns against parts of the body, destroying the very cells and tissues it is meant to protect.
AdvertisementScripps Research Professor of Immunology and Microbial Science Dwight Kono demonstrated that three proteins, called Toll-like receptors (TLRs), are necessary for this autodestruction to occur.
TLRs are proteins found in immune cells that normally help stimulate the initial response of the immune system to foreign pathogens. Humans have 10 different types of TLRs.
While, some of them sit on the surface of immune cells, other TLRs-TLR 3, TLR7, and TLR 9-reside inside immune cells, in a compartment known as the endolysosome, where bits of foreign substances usually end up.
By engineering mice that lack either TLR 7 or TLR9, scientists have gathered evidence that these TLRs may play a role in the disease.
"Earlier studies had strongly suggested that endolysosomal TLRs were important, but if you eliminate one or the other you do not get a huge effect," said Kono.
To answer this question, Kono and colleagues took advantage of strains of laboratory mice prone to lupus. These mice spontaneously develop many of the same signs and symptoms as humans with the disease.
The next step was to eliminate TLR 3, TLR 7, and TLR 9 in these lupus-prone mice.
They found that the mice lacking functioning TLR 3, TLR 7, and TLR 9 did not develop lupus.
"It seems like these three TLRs are absolutely required for optimal autoantibody production," said Kono.
"This is an important finding that builds on results obtained by other groups," Kono added.
The study is published in the Early Edition of the Proceedings of the National Academy of Sciences (PNAS).