Immune-regulating nanoparticles prevent arthritis in susceptible mice
Autoimmune diseases are a common health problem, and while system-wide immune suppression can help relieve symptoms, this can cause other complications. In a new study, scientists at Scripps Research developed nanoparticles that can selectively target problematic immune cells, to significantly delay and even prevent arthritis in mice.
The immune system is the body’s first and strongest line of defense against disease, but it can become a bit overzealous at times and begin attacking healthy cells and tissues. This can trigger a range of autoimmune diseases, which can be treated with drugs that suppress the immune system. But of course, that leads to other complications, such as increased risk from infectious diseases.
For the new study, the Scripps team investigated a technique that only shuts down the immune cells causing the autoimmune issues, leaving others to their important duty of fighting off true health threats. Some autoimmune diseases, such as rheumatoid arthritis, are triggered by a single protein in the body, known as a “self-antigen,” and these were the focus of the study.
B cells make antibodies to specific antigens – usually foreign ones, but also self-antigens in the case of autoimmune diseases. They can effectively be switched off if they encounter the antigen they target at the same time as another molecule that binds to a receptor called CD22. So, the Scripps team designed nanoparticles that contain both the antigen and a CD22-binding molecule.
The nanoparticles also contained rapamycin, a drug that stimulates the production of regulatory T cells (T regs) that, as the name suggests, suppress other immune cells that might be going rogue. All of these ingredients together should help the nanoparticles counter an autoimmune response from specific B and T cells, without requiring a full shutdown of the immune system.
The team tested the nanoparticle therapy in mice. First, they demonstrated that it was able to prevent the animals’ immune systems from mounting an attack against a chicken protein called ovalbumin that would normally set off a strong response. Then it was tested against an autoimmune disease, in mice engineered to be predisposed to arthritis by attacking a self-antigen called GPI.
The researchers treated mice from the age of three weeks with nanoparticles that taught their immune systems to tolerate GPI. And sure enough, the therapy significantly delayed the onset of arthritis, signs of which would normally begin appearing a few weeks later without treatment. Even more encouraging, one third of the treated mice still showed no signs of arthritis by the end of the experiment 300 days later, which represents a large chunk of the mouse lifespan.
Closer inspection showed that the treatment was working as hoped. The mice had greatly reduced production of anti-GPI antibodies, and much higher T reg populations.
“We were able to ‘cure’ a third of these animals in this early demonstration, and I think there's the potential to combine our nanoparticles with other immune modulator treatments to make it even more effective,” said James Paulson, senior author of the study. “So that will be our next step – as well as demonstrating our technology against other autoimmune diseases caused by unwanted immune responses to a self-antigen.”
The research was published in the journal ACS Nano.
Source: Scripps Research