Nanoparticles like the one above are increasingly used for therapeutic purposes. This nanoparticle is covered with an innocuous polyethylene glycol coating. Source: WeSrch Wiki, Credit: Richard Moore).
By Kevin Kang
Contemporary therapies for allergy-mediated diseases like allergic asthma and food allergies are sub-optimal (1). These diseases are caused by the body’s hypersensitive reactions to otherwise innocuous environmental proteins. Present treatments, which involve administering escalating doses of a harmful allergen can be risky and prolonged. Allergens are environmental proteins that cause allergic reactions; when introduced into a patient’s body, allergens are attacked by the patient’s immune system. More specifically, exposure to an allergen results in activation of allergen-specific helper T cells that start a complex immune inflammatory reaction. However, this aggressive inflammatory response damages the patient’s tissues. Any later exposure to the allergen protein would lead to a similarly hypersensitive harmful reaction. This overreaction could manifest itself in many ways such as asthmatic symptoms and hives.
However, if the allergen that ordinarily elicits a harmful allergic reaction could be presented to the immune system in a way that the immune system becomes tolerant of the allergen, allergic diseases could be greatly alleviated. Using this concept, researchers in Northwestern University exposed experimental mice to harmful allergen proteins that were hidden inside a friendly shell of biodegradable nanoparticles (2). The nanoparticles are coated with an FDA-approved biopolymer called PLGA, which consists of lactic acid and glycolic acid (2). This novel nanoparticle-based method helps create tolerance in the host’s immune system and holds great promise for mitigating allergic diseases.
According to senior author Dr. Stephen Miller, no matter what kind of allergy and no matter what kind of allergen is causing the allergic reaction, the allergen can be inserted into a nanoparticle, which can then be presented to the host’s helper T cells (2). By presenting the allergen in a nanoparticle, the helper T cells no longer consider the allergen a threat, and the harmful inflammatory response is aborted (2).
This concept has been confirmed in mice models, where allergen-loaded nanoparticles have been introduced into the blood streams of mice. The mouse’s immune system does not recognize the particle as a threat and instead views it as innocuous debris. Cells of the immune system called macrophages then consume the nanoparticle with its underlying hidden allergens and remove it from circulation (1). Macrophages essentially “reset” the immune system by presenting the allergen or antigen to other immune cells, which no longer attack the antigen after presentation (2).
In the experiments conducted at Northwestern, scientists made experimental mice allergic to an egg protein by generating antibodies against the egg protein in the mice’s blood. When the egg protein was reintroduced into these mice’s lungs, they responded with an allergic response similar to asthma. However, after the above nanoparticle-based treatment using egg protein-loaded particles, the mice no longer exhibited an allergic response to the egg protein (1).
This approach has an additional benefit: it creates a more balanced immune system by increasing the number of regulatory T cells, which are important cells responsible for recognizing airway allergens as innocuous (1). Thus, this method of introducing allergens inside protective nanoparticles prevents the recruitment of helper T cells and instead increases the number of calming, reaction-stopping regulatory T cells. Although the above study was conducted in mice, this nanoparticle-based technology is already being tested in human clinical trials striving to alleviate autoimmune diseases like celiac disease and multiple sclerosis (2).
References:
- Charles B. Smarr, Woon Teck Yap, Tobias P. Neef, Ryan M. Pearson, Zoe N. Hunter, Igal Ifergan, Daniel R. Getts, Paul J. Bryce, Lonnie D. Shea, and Stephen D. Miller. 2016. Biodegradable antigen-associated PLG nanoparticles tolerize Th2-mediated allergic airway inflammation pre- and postsensitization. PNAS, DOI: 1073/pnas.1505782113
- Northwestern University. (2016, April 18). Nanoparticle acts like Trojan horse to halt asthma: New technology also can be used to turn off peanut and other food allergies. ScienceDaily. Retrieved April 30, 2016 from sciencedaily.com/releases/2016/04/160418161000.htm