Starved immune cells shut down the allergic response, researchers discover

Innate lymphoid cells require key nutrients to launch an immune response. When researchers starved immune cells of these nutrients, the cells’ inflammatory response was dimimished, according to a study published online April 4, 2016 in the journal Nature Immunology.

This finding offers the potential to treat a wide range of inflammatory and allergic conditions, including hay fever, food allergies, asthma, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis, the researchers predicted.

“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,” said senior investigator David Artis, PhD, Director of the Jill Roberts Institute for Research in Inflammatory Bowel Disease and the Michael Kors Professor of Immunology at Weill Cornell Medicine, in New York, NY.

Scientists have known that innate lymphoid cells (ILCs) are involved in promoting allergic diseases in the lungs and other organs. In this study, the researchers discovered that inhibiting the activity of the enzyme arginase-1 (Arg1) in the lungs of mice changed the metabolism within ILCs, which cut off a critical supply of nutrients.

The researchers discovered that disruption of this metabolic pathway shut down the pathologic immune responses that would otherwise promote allergic inflammation in the animals’ lungs.

“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,” Dr. Artis said.

In this study, the researchers developed mice genetically engineered to delete Arg1 in ILCs. They then administered the allergen papain (derived from the papaya plant) into the nostrils of the genetically-engineered mice. They found that the mice were unable to mount an allergic response, which in turn prevented the development of lung inflammation.

Next, the researchers showed that the lack of an allergic response was due to the missing Arg1 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.

ILCs contribute to tissue inflammation and immunity in multiple organs, not just the lung, the researchers noted. So, therapies that alter the Arg1 metabolism of these immune cells may offer relief for inflammation caused by a variety of allergic diseases, they reasoned.

“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,” said first author Laurel Monticelli, PhD, a postdoctoral associate in Dr. Artis’ lab.