Toll-like Receptors "Collecting" Increasing Recognition in Lupus Research

Recently, the Lupus Research Institute (LRI) recognized Toll-like receptors as a rapidly growing area of lupus research, reporting on two recently published studies. Just days later, Toll-like receptors are making news again as yet another major LRI-funded discovery is published with important implications for developing new treatments and a cure for lupus.

Proteins know as Toll-like receptors (TLRs) found on cells of the immune system protect us against a broad range of infections by detecting the presence of invading microorganisms and instructing the immune system to attack. But in some people, TLRs incorrectly react to harmless components of the body’s own cells as if they were viruses. As shown in previous studies by LRI-funded scientists and others, these misdirected attacks on ‘self’ might be one of the earliest triggers for autoimmune diseases such as lupus.

With an LRI Novel Research Grant, Dr. Gregory Barton and colleagues at the University of California at Berkeley asked why mistakes by TLRs leading to autoimmunity are the exception rather than the rule. They found a new biological process that might reduce the chance that cells of the immune system will attack the body.

Dr. Barton’s team uncovered how two of the TLR proteins called TLR9 and TLR7, known to cause lupus in mice, are ‘chaperoned’ within cells by other, protective proteins. These chaperones strictly control the activity of TLRs, limiting their opportunities to cause harm. The findings are published in eLIFE, a new open access journal established and run by leading scientists.

Based on these promising results, Dr. Barton plans to further investigate whether patients with lupus have genetic defects in the chaperones that might prevent them from doing their job, allowing TLRs to run amok and to trigger disease.

This follow up work is funded by Dr. Barton’s new $1 million Distinguished Innovators Award from the LRI. He will delve deeper, seeking to understand how TLRs trigger lupus and how this could be prevented. “Identifying the players that normally keep TLRs in check can help us understand why these proteins trigger disease in certain people,” explained Dr. Barton.  “Ultimately, this knowledge will enable the development of treatments targeting TLRs or proteins that control TLR function.”