To gain insights into Type 2 immune responses—the immune responses associated with allergies, asthma, and chronic obstructive pulmonary disease—scientists at Rutgers University have been taking a close look at helminths, parasitic worms that are transmitted to humans from contaminated soil. Helminths are generally unwelcome. Besides causing infections, they can initiate Type 2 immune responses that get out of control. Yet the worms can, when administered at controlled doses, prevent the development of inflammatory disease states. In fact, helminths have been used to treat irritable bowel disease and ulcerative colitis—even allergies.
The Rutgers team led by assistant professor Mark C. Siracusa, PhD, recently investigated how the Type 2 immune response may involve the expression of a neuropeptide, neuromedin B (NMB), that can prevent overactive immune responses and damaging inflammation. Siracusa and colleagues detailed their findings in an article (“Basophils prime group 2 innate lymphoid cells for neuropeptide-mediated inhibition”) that appeared in Nature Immunology.
The article discusses how NMB may reflect the long association between helminths and mammals. That is, the article considers whether the worms may have “taught” the immune systems of its hosts, including humans, not to overreact. The article also explores whether the study of helminth-influenced immune mechanisms could be relevant to the search for therapeutics for inflammatory diseases.
“We demonstrate that helminth-induced group 2 innate lymphoid cell (ILC2) responses are exaggerated in the absence of basophils, resulting in increased inflammation and diminished lung function,” the article’s authors wrote. “Additionally, we show that ILC2s from basophil-depleted mice express reduced amounts of the receptor for NMB.”
The article emphasized this critical point: “NMB stimulation inhibited ILC2 responses from control but not basophil-depleted mice, and basophils were sufficient to directly enhance NMB receptor expression on ILC2s.” The article also pointed out that the NMB protein can stop the type of inflammation that occurs in diseases like asthma, allergies, chronic fibrosis, and COPD.
“For many years, the mechanism through which the body shuts down an inflammatory response to heal itself after worm infections remained poorly understood,” said Siracusa, senior author of the Nature Immunology article. “Our study provided that understanding and a hope for possible treatments using NMB, which has great potential to treat inflammatory diseases like asthma, allergies, and COPD.”
COPD is the third most common cause of death among inflammatory diseases and allergies the sixth in the United States.
“Scientists previously thought the immune system was capable of regulating itself to resolve inflammation to prevent tissue damage,” Siracusa noted. “However, emerging work is beginning to reveal that complex interactions between the immune system and the nervous system serve to restrict inflammation and promote health.”
A patent cooperation treaty (PCT) patent application was filed by the Rutgers Office of Research Commercialization. The next steps for researchers include developing drugs using the protein to treat diseases like asthma, COPD, and allergies.