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How Molecular Rules Govern Autoimmune Disorders

  Bundles with Right DNA Spacing Can Amplify Immune Response
  Bundles with the right DNA spacing
can amplify immune response.
Image: Courtesy of Dr. Gerard C. L. Wong

An international team led by UCLA researchers has identified an unexpectedly general set of rules that determine which molecules can cause the immune system to become vulnerable to the autoimmune disorders lupus and psoriasis.

Autoimmune diseases occur when the body attacks itself because it fails to distinguish between host tissue and disease-causing agents, or pathogens. When a healthy person is infected by a virus, viral DNA can activate immune cells via a receptor called TLR9. The receptor triggers the cells to send signaling molecules called interferons to initiate a powerful defensive response. In people with lupus or psoriasis, these cells are activated by their own DNA, or self-DNA.

Using synchrotron X-ray scattering and other techniques, the researchers determined that a broad range of molecules can organize self-DNA into a liquid crystalline structure that binds strongly to the TLR9 receptors — like the teeth on either side of a zipper. This structure protects the DNA from becoming degraded and greatly amplifies the body’s immune response.

Synchrotron X-ray scattering utilizes a particle accelerator to generate X-ray beams that allow researchers to determine how atoms and molecules are organized into different structures. “Our research has identified a set of rules that tell us what types of molecules or materials can set off this aspect of the immune system,” says Gerard C. L. Wong, PhD, professor of bioengineering and chemistry. “This new knowledge will make it easier to design new therapeutic strategies.”

“Liquid-crystalline Ordering of Antimicrobial Peptide-DNA Complexes Controls TLR9 Activation,” Nature Materials, June 2015


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