DNA-TLR9 Zipper Triggers Autoimmune Response

A zipper-like arrangement of DNA can bind strongly to the receptor TLR9 and trigger a strong immune response.

AsianScientist (Jun. 22, 2015) – In a paper published in Nature Materials, scientists have uncovered a simple rule which governs the strong activation of the immune receptor TLR9, thereby determining which molecules can cause the immune system to become vulnerable to the autoimmune disorders such as lupus and psoriasis.

Autoimmune diseases strike when the body attacks itself because it fails to distinguish between host tissue and disease-causing agents, or pathogens. Two such disorders are lupus which damages the skin, joints and organs, causing rashes, hair loss and fatigue; and psoriasis, which causes rashes, lesions and arthritis, and creates an increased risk for cancer and diabetes.

When a healthy person is infected by a virus, viral DNA can activate immune cells via a receptor called TLR9. The receptor triggers immune cells known ad dendritic cells to send signaling molecules called interferons that 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 computer simulations, the team including researchers from the University of Science and Technology of China and Beijing University of Chemical Technology examined the hypothesis that the spacing of DNA in a liquid-crystal complex correlates with the strength of interferon response in dendritic cells.

They determined that a broad range of both organic and inorganic 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.

“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, this new knowledge will make it easier to design new therapeutic strategies to control immune responses,” said Professor Gerard Wong, corresponding author of the study from the University of California, Los Angeles.

The article can be found at: Schmidt et al. (2015) Liquid-Crystalline Ordering Of Antimicrobial Peptide–DNA Complexes Controls TLR9 Activation.


Source: Chinese Academy of Sciences; Photo: UCLA Engineering.
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