UCLA recently produced a news release on research published in journal of Nature Communications. Recent research centers on autoimmune disease inflammation. Those struggling with psoriasis or hidradenitis suppurativa or other autoimmune diseases face what can be debilitating conditions caused by inflammation. The UCLA-led team discovered a certain molecule found in the immune system—LL37—play an important but unexpected role in revving up the body’s self-defense response. The recent discovery may help researchers understand how to control the immune systemin more precise ways. The UCLA press release notes that the immune system is home to cells that detect attacks by viruses and bacteria. They contain toll-like receptors—a class of proteins that act as early warning sensors by rapidly detecting molecular patterns that are commonly found in invading foreign entities. However these toll-like receptors, in some cases, detect the body’s own DNA which leads to havoc on the immune system.
The immune system produces “first responder” molecules called antimicrobial peptides. LL37 is one of these. There has been evidence that LL37 molecules strengthen the immune response by working together with toll-like receptors. Ernest Lee, study co-author noted “but there was confusion as to how LL37 molecules could control toll-like receptors and direct the immune system to attack when it detects the body’s own DNA.”
The UCLA-led team sought to understand this mechanism by first learning more about LL37’s behavior. By leveraging a technique called synchrotron small-angle x-ray scattering—enabling them to observe objects as small as one one-hundred-billionth of a meter! Combining this with computer modeling they produced three-dimensional representations of the LL37 molecules. The researchers were thereafter able to observe the LL37 molecules forms “into a kind of linear backbone.” They found that “the large number of repeating DNA units binding to multiple toll-like receptors is what revs up inflammation, the body’s immune response.”
Thereafter the researchers incubated mouse and human immune cells with an LL37-DNA complex. They were able to design and observe “a highly active immune response” confirming that the hypothesis that “LL37-DNA complex was responsible for activating the immune system.” Researchers now possess new insight into LL37 role and offers new target use in studies focusing on controlling immune system response.
University of Texas Austin
Jeremy Di Domizio
Lausanne University Hospital
University of Science and Technology of China