Optogenetic tool controls inflammation, with potential for targeted inflammatory disease therapy

An optogenetic tool activated by UV light could allow better study of inflammation and the immune system.

Content Dam Bow Online Articles 2016 12 Uvrays460 Web

Seeking a better way to study inflammation and the immune system, a team of researchers at Cornell University (Ithaca, NY) has developed an optogenetic tool activated by ultraviolet (UV) light to control inflammation. The method could someday be used as a targeted therapy for inflammatory diseases like asthma, multiple sclerosis, rheumatoid arthritis, colitis, and Crohn's disease, while minimizing side effects to healthy tissues.

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The researchers created a chemical probe that inhibits a reaction mediated by enzymes called histone deacetylases (HDACs). These enzymes regulate genes that turn on when the immune system is challenged and promote inflammation. HDACs also have inhibitors that suppress this inflammatory response and the probe specifically activates these inhibitors, but only in the presence of optogenetic (a technique that uses light to control cells in living tissue) stimulation via UV light. This is especially useful since HDACs are ubiquitous and have other biological effects, and most drugs affect the entire system, leading to unintended consequences.

Content Dam Bow Online Articles 2016 12 Uvrays460 Web
This fluorescence image demonstrates how light-activated chemical probes developed by the Chang Laboratory were used to selectively turn off inflammatory activities of immune cells that were irradiated with light (denoted by the dotted line). Irradiated cells are shown in red, and inflammatory molecules are shown in cyan. (Courtesy of Bibudha Parasar)

"If you turned off all the HDACs in the body, you would probably be hitting a lot of pathways that you didn't want to turn off," says Pamela Chang, assistant professor of microbiology and immunology, and the senior author of a paper describing the work. "We can control when and where we turn off the HDACs using light. The idea is that you can actually target the tissue that has chronic inflammation and regulate it by selectively inhibiting HDACs in the tissue that's affected."

Photodynamic therapies are being developed and have existing infrastructure in the clinic for the potential use of the new tool to inhibit inflammation in patients with inflammatory diseases, Chang says.

Bibudha Parasar, a graduate student in Chang's lab, is the paper's first author.

Full details of the work appear in the journal Chemical Science; for more information, please visit http://dx.doi.org/10.1039/c6sc03702j.

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