APR 29, 2016 9:30 AM PDT

Can starving these cells stop a range of allergies?

Starving immune cells of key nutrients thwarts their ability to launch an allergic response, according to new research.
 
"This report gives us new mechanistic insight to understand how we might be able to design more selective drugs that specifically target ILCs to treat a range of allergic diseases," says David Artis.

The findings illuminate how nutrients help drive tissue inflammation caused by the immune system—an insight that could lead to new treatments for a wide range of inflammatory conditions from hay fever and food allergies to asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF).

Scientists know from both animal model systems and patient-based studies that a class of immune cells, called innate lymphoid cells (ILCs), play a role in promoting allergic diseases in the lung and other organs. In this new study, published in Nature Immunology, investigators discovered that inhibiting the activity of an enzyme called Arginase-1 changes the metabolism within ILCs, cutting off a critical nutrient supply.

Furthermore, disrupting this metabolic pathway in mice shuts down pathologic immune responses that would otherwise promote allergic inflammation in the lung.

“These findings are very exciting and propel us to look deeper into how the immune system is regulated in the context of health and chronic inflammatory diseases,” says senior investigator David Artis, director of the Jill Roberts Institute for Research in Inflammatory Bowel Disease and professor of immunology at Weill Cornell Medicine.

“This report gives us new mechanistic insight to understand how we might be able to design more selective drugs that specifically target ILCs to treat a range of allergic diseases.”
 

A new target for treatment?


The researchers, led by first author Laurel Monticelli, a postdoctoral associate in Artis’ lab, used mice genetically engineered to delete the gene for Arginase-1 in ILCs, leaving the rest of the immune system intact. They found that when the genetically engineered mice were exposed to an allergen called papain, which is derived from the papaya plant, the mice were unable to mount an allergic response, which in turn prevented the development of lung inflammation.

Monticelli and her colleagues went on to show that the lack of an allergic response was due to the missing Arginase-1 enzyme, which normally provides energy to the cells by breaking down the amino acid arginine into other metabolic nutrients needed by ILCs. Without these nutrients, the ILCs were essentially starved and became unable to proliferate or function.

To explore the potential clinical implications of these findings for human disease, the investigators analyzed lung tissue samples from patients with the chronic inflammatory lung diseases COPD or IPF. The researchers studied the human ILCs within these inflamed tissues and found evidence that these cells expressed Arginase-1.

“While these are still early days in this research, our patient-based analysis, coupled with our mouse model studies, suggests altering Arginase-1 metabolism within these innate immune cells may offer a therapeutic target for multiple inflammatory diseases,” Monticelli says.
 

Allergies cost over $18 billion a year


Allergies are the sixth-leading cause of chronic illness in the United States with an annual cost in excess of $18 billion. More than 50 million Americans suffer from allergies each year. The investigators’ findings have implications for a broad range of allergic diseases. One of these conditions is the “allergic march,” a medical phenomenon in children in which one allergic disease, such as eczema, rapidly progresses to multiple allergic diseases including asthma and life-threatening food allergies.

Because ILCs have been shown to contribute to tissue inflammation and immunity in multiple disease settings, not just the lung, the investigators said it is possible that therapies aimed at changing the Arginase-1 metabolism of these cells may offer relief for inflammation caused by a variety of allergic diseases.

The National Institutes of Health, the Burroughs Wellcome Fund, the Crohn’s and Colitis Foundation of America, the Edmond J. Safra Foundation/Cancer Research Institute, the National Science Foundation, the Robert Wood Johnson Foundation, the Thoracic Surgery Foundation, and the German Research Foundation supported the work.

Source: Cornell University

This article was originally published on futurity.org.
About the Author
  • Futurity features the latest discoveries by scientists at top research universities in the US, UK, Canada, Europe, Asia, and Australia. The nonprofit site, which launched in 2009, is supported solely by its university partners (listed below) in an effort to share research news directly with the public.
You May Also Like
JAN 20, 2020
Cell & Molecular Biology
JAN 20, 2020
Using Modified Red Blood Cells As a Drug Delivery System
For a drug to be effective, it has to get to the right place to exert its impact....
JAN 23, 2020
Cell & Molecular Biology
JAN 23, 2020
Scientists Engineer Venom-Producing Organoids
Snake venom is also a source of therapeutics, and a potential source of new medicines....
FEB 09, 2020
Cell & Molecular Biology
FEB 09, 2020
Switching Inflammation Off at the Molecular Level
While chronic inflammation is a natural result of getting old, experiencing stress, and toxin exposure, it's been theorized to be the basis for many chronic diseases....
FEB 11, 2020
Neuroscience
FEB 11, 2020
Soybean oil Causes Genetic Changes in Mouse Brain
Source: Hypothalmus and limic system   Soybean oil is used for cooking fast food, in packaged products, and to feed livestock, making it the most wide...
MAR 04, 2020
Genetics & Genomics
MAR 04, 2020
DNA Fragments and Cartilage Recovered From 75-Million-Year-Old Dinosaur Bones
An international team of researchers has analyzed cartilage from a baby duckbilled dinosaur, and they have identified bits of preserved proteins and what seems to be chromosomes....
MAR 03, 2020
Cancer
MAR 03, 2020
New technique maps tissue development and tumors
Research published recently in the Proceedings of the National Academy of Sciences details the development of a new technique that is capable of mappi...
Loading Comments...