Retraining Innate Immune Cells to Combat Autoimmune Diseases

 Peter Deak

Every day, your immune system comes across tens of thousands of foreign organisms. It’s up to the innate immune cells – a set of white blood cells that act as the sentries of the immune system – to screen these organisms to determine what’s dangerous, but perhaps more importantly, what can be ignored.

“Generally, our innate immune cells have certain chemical cues that can identify self from non-self, and when they see something that’s not harmful, they can say ‘don’t attack this.’ —otherwise we’d be fighting everything,” explained Peter Deak, PhD , assistant professor of chemical and biological engineering at Drexel Engineering. “But occasionally, they see something innocuous – like our own cells – as dangerous, and attack.”

This malfunction is the basic definition of an autoimmune disease, and Deak’s research could unlock a unique way to fight them.

“My work right now is specifically looking at multiple sclerosis, because there’s solid evidence about how that works,” he said. “The innate immune cells in the brain see proteins in nerve cells and think they’re pathogenic, and they tell the body to attack them, which creates inflammation, which in turn drives more immune response, creating more inflammation, and it snowballs. So, if we can reconstruct the innate immune cells to be more tolerant then we can cut that off from just sort of spiraling out of control.”

Deak’s research recently received support from the Margaret Q. Landenberger Research Foundation, a non-profit private organization which focuses its support on promising early-stage medical researchers. If successful, his research could lead to new therapeutics for autoimmune diseases that could target the source of the problem, a vast improvement over current treatments.

“The main problem in that the treatments that exist now are basically just broad spectrum immunosuppressants, which work to an extent, but you have to take them for the rest of your life, and because you’re suppressing everything, you’re more at-risk for cancer, infection and almost every other disease out there,” Deak explained. “If we can target the one protein that causes the autoimmune response, we could potentially make a memory response that’s tolerant, and that’s kind of the Holy Grail of autoimmune treatment.”

Deak sees his research as a cross between engineering, chemistry and immunology.

“I’m kind of wearing three hats,” he said. “I look at how these molecular compounds interact with dendritic cells, which are our primary antigen presenting cells, and I look for specific markers that signify whether they will fight the compound or have a tolerant reaction. Then I have to figure out the most effective way to deliver that compound to the body.”

The difficulty in this final step is that, in the past, therapeutics were delivered with an immunosuppressant. This would create a short-term tolerance, but the body didn’t learn and replicate the instructions to remain tolerant, and if the immunosuppressants were stopped, so too was the fix.

“What I found during my post-doc is that, if you combined an inhibitory signal with an immunostimulant – something like you would normally put in like a vaccine – that actually caused the dendritic cells to be tolerant, but also to continue to replicate and actively present antigen,” he said. “But now I'm really looking for a more sophisticated and simple solution, because the first one I found was a little complex, requiring multiple drugs to be delivered at different times, so it couldn’t be translated into a realistic therapy.”

Deak’s research has been published in Cell Reports, Biomaterials and other peer-reviewed journals. He is currently building a team of graduate and undergraduate students to help him further his research.