Tiny Particles Carrying Myelin Antigens Seen to Restore Immune Tolerance in MS Mice Model
Researchers managed to change the immune system — replacing inflammation with immune tolerance — in a mouse model of multiple sclerosis (MS) using so-called quantum dots, or nano-sized particles carrying pieces of myelin.
Experiments with this advanced technological solution may help researchers design MS therapies that are based on promoting regulatory T-cells rather than suppressing those that cause inflammation.
Regulatory T-cells are capable of controlling the inflammatory response against myelin that occurs in MS (myelin is the protective cover surrounding neurons), while keeping the health-promoting work of the immune system intact.
“Engineering technologies aimed at autoimmune disease could pave the way for new treatment options,” Christopher Jewell, an assistant professor at the Fischell Department of Bioengineering at the University of Maryland and principal investigator on the study, said in a press release.
“However, in order to develop next-generation therapies, bioengineers need basic insight into the specific features that are critical to therapy design,” Jewell added.
The study, “Engineering Immunological Tolerance Using Quantum Dots to Tune the Density of Self-Antigen Display,” showed that processes that drive inflammation or immune tolerance are influenced by the concentration and form of antigens.
Antigens are tiny pieces of proteins, displayed as flags on the surface of all cells. The immune system uses these flags to distinguish between self and non-self cells or structures. When a foreign antigen, like bacteria or a virus, is spotted, an immune reaction ensues. But in MS, the immune system mistakenly reacts to myelin antigens.
With MS as with other autoimmune diseases, researchers are still searching for the reason why the immune system makes this mistake.
Published in the journal Advanced Functional Materials, the study showed that when many quantum dots were loaded with a few myelin antigen molecules each, tolerance emerged. In contrast, exposing mice to a few quantum dots that were heavily loaded with antigens promoted inflammation.
The quantum dots are an excellent tool to study these processes, as they tick many of the boxes for technical requirements. They are sufficiently small to travel lymph vessels and accumulate in lymph nodes. Researchers can also design them so that they hold a precisely defined number of antigens.
Importantly, they are fluorescent, making it possible for researchers to track them as they travel through the body.
“One of our exciting findings is that tolerance and elimination of paralysis in a pre-clinical mouse model was much better when myelin peptides were displayed on many quantum dots at a low density of 25 per dot, instead of fewer quantum dots displaying the same number of peptides but at a high density of 65 per dot,” Jewell said.
Finding an optimal composition of antigens on quantum dots provided some quite striking results. Mice so debilitated by the disease that they were partly paralyzed became better — the treatment nearly eliminated paralysis, the researchers noted in the report.
“Developing specific knowledge or design guidelines such as these might enable more selective — and effective — therapies to treat MS and other diseases,” Jewell said.
“Generally, because the human body is so complex, discoveries in medicine have relied on trial and error. But, by using rational design approaches — understanding what each piece of a potential therapeutic controls — we have the potential to transform how disease is tackled,” he concluded.