Cargo-carrying red blood cells alleviate autoimmune diseases in mice

March 6, 2017
blood cells
Scanning electron micrograph of blood cells. From left to right: human erythrocyte, thrombocyte (platelet), leukocyte. Credit: public domain

Using red blood cells modified to carry disease-specific antigens, scientists in the laboratories of Hidde Ploegh (former Whitehead Member, currently Boston Children's Hospital) and Harvey Lodish (Whitehead Founding Member) have prevented and alleviated two autoimmune diseases—multiple sclerosis (MS) and type 1 diabetes—in early stage mouse models.

"This is a very promising step in the development of therapies for autoimmune diseases," says Lodish, who is also a professor of biology and a professor of at MIT. "If this type of response is also true in humans, then it could make a lot of these therapies possible for these diseases and similar conditions."

Inappropriate immune responses cause scores of autoimmune diseases—from rheumatoid arthritis to to inflammatory bowel disease—in which the body destroys its own cells. The National Institutes of Health estimates that autoimmune diseases affect more than 23 million Americans. These conditions are commonly treated with immunosuppressants to keep a patient's overactive immune response in check. However, these drugs also indiscriminately dull the immune response to pathogens.

Using bits of proteins from the offending cells—antigenic peptides—researchers have retrained the immune system to ignore the antigens that trigger inappropriate immune responses. This method, called tolerance induction, shows promise, but the technique is fraught with problems, including delivering the antigenic peptides to their destination before they are degraded or beset by .

To sidestep many of these issues, the labs of Lodish and Ploegh have pressed red into service.

Red blood cells are particularly well-suited for the delivery of molecules throughout the body. Not only do these cells quickly access almost every tissue, they are also recycled every month in mice and four months in humans without triggering an immune response against them. In previous research, the team attached biotin (a chemical tag) and antibodies to red blood cell using a method developed by Ploegh's lab called "sortagging".

The current work, which is described online this week in the journal PNAS, uses cargo-laden red blood cells to intercede in . Novalia Pishesha, an MIT Biological Engineering graduate student in the Lodish and Ploegh labs, drew blood from a mouse, used sortagging to decorate the red blood cells with the antigens that trigger the harmful , and transfused the altered red blood cells back into mouse models of type 1 diabetes and MS. The entire process can be completed in about an hour.

In mice, the transfusions reduced symptoms of disease and even a single injection prior to the onset of disease could prevent further symptoms.

Although antigenic peptides can be effective in stimulating the induction of tolerance, the mechanism responsible is not well understood at the cellular and molecular levels.. "Essentially what we're doing is hijacking the clearance pathway, such that the foreign antigen masquerades as the red blood cells' own, such that these antigens are being tolerated in the process," says Pishesha, who is also the first author of the PNAS paper.

For Ploegh, the research could lead to future insights into how the immune system regulates itself and how that sometimes goes awry. As a cautionary note, he points out that red blood cells used in the experiment are not "immunologically inert".

"The Kell protein, which we use as an anchor point for many of our modifications, is a blood group antigen, and by its very nature shows that the immune system can distinguish red blood cells from genetically disparate individuals," says Ploegh. "This [technique used by Pishesha] may be an interesting way to explore how the distinguishes self from non-self."

Explore further: Scientists identify factor that may trigger type 1 diabetes

More information: Engineered erythrocytes covalently linked to antigenic peptides can protect against autoimmune disease, PNAS (2017). DOI: 10.1073/pnas.1701746114

Related Stories

Scientists identify factor that may trigger type 1 diabetes

February 11, 2016
A team of researchers, led by investigators at the University of Colorado School of Medicine, have identified a new class of antigens that may be a contributing factor to type 1 diabetes, according to an article published ...

Engineered red blood cells could carry precious therapeutic cargo

June 30, 2014
Whitehead Institute scientists have genetically and enzymatically modified red blood cells to carry a range of valuable payloads—from drugs, to vaccines, to imaging agents—for delivery to specific sites throughout the ...

How autoimmune disease is prevented—mechanism discovered

November 1, 2016
A previously unknown safety mechanism in our immune system keeps the body free from autoimmune diseases. Researchers from Karolinska Institutet have discovered that a cell in our inherited immune system can prevent our adaptive ...

Noninvasive imaging of immune system detects tumors, could monitor therapeutic response

April 20, 2015
A novel approach that allows real-time imaging of the immune system's response to the presence of tumors—without the need for blood draws or invasive biopsies—offers a potential breakthrough both in diagnostics and in ...

Modified antibodies trigger immune response, point to novel vaccine design strategies

January 7, 2013
In an approach with the potential to aid therapeutic vaccine development, Whitehead Institute scientists have shown that enzymatically modified antibodies can be used to generate highly targeted, potent responses from cells ...

Scientists successfully create blood from skin cells

November 21, 2016
Researchers in Singapore have artificially generated new mouse blood and immune cells from skin cells. This is a significant first step towards the eventual goal: the engineering of new human blood cells from skin cells or ...

Recommended for you

Genetic variants found to play key role in human immune system

August 16, 2017
It is widely recognized that people respond differently to infections. This can partially be explained by genetics, shows a new study published today in Nature Communications by an international collaboration of researchers ...

Biophysics explains how immune cells kill bacteria

August 16, 2017
(Tokyo, August 16) A new data analysis technique, moving subtrajectory analysis, designed by researchers at Tokyo Institute of Technology, defines the dynamics and kinetics of key molecules in the immune response to an infection. ...

Study identifies a new way to prevent a deadly fungal infection spreading to the brain

August 16, 2017
Research led by the University of Birmingham has discovered a way to stop a deadly fungus from 'hijacking' the body's immune system and spreading to the brain.

How a nutrient, glutamine, can control gene programs in cells

August 15, 2017
The 200 different types of cells in the body all start with the same DNA genome. To differentiate into families of bone cells, muscle cells, blood cells, neurons and the rest, differing gene programs have to be turned on ...

Scientists identify gene that controls immune response to chronic viral infections

August 15, 2017
For nearly 20 years, Tatyana Golovkina, PhD, a microbiologist, geneticist and immunologist at the University of Chicago, has been working on a particularly thorny problem: Why are some people and animals able to fend off ...

Clustering for health

August 15, 2017
When functioning appropriately, the immune system protects against multiple threats such as pathogens, disease-causing microbes, and tumors. However, when the immune system is inappropriately activated, it attacks the body, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.