An ILC2’s job is to make signaling molecules (called cytokines) that quickly alert other immune cells to react to a pathogen. Unfortunately, ILC2s sometimes over-react and respond to harmless environmental allergens. In these cases, ILC2s churn out cytokines that drive mucus production and inflammation in the lungs. All this swelling and mucus leads to hypoxia.
As they report in Journal of Experimental Medicine, ILC2s respond to hypoxia as well, adding to the lung damage already caused during an asthma attack. “That hypoxia may then contribute further to inflammation,” says Kronenberg.
The next step was to figure out exactly how epithelial cells activate ILC2 during hypoxia. LJI Postdoctoral Fellow Jihye Han, Ph.D., led the work to uncover an unexpected culprit: adrenomedullin (ADM). ADM is known for its role in helping blood vessels dilate, but until now it had no known role in immune function.
Kronenberg was surprised to see ADM involved—but not shocked. “We’re finding that many molecules with no previously known role in the immune system can also be important for immune function,” says Kronenberg. “We need to understand that more generally.”
The researchers showed that human lung epithelial cells exposed to hypoxia also produced ADM. This means ADM or its receptor could be targets for treating inflammatory and allergic lung diseases.
The challenge is to find a balance between dampening the harmful immune response without leaving the body vulnerable to infections. Kronenberg points out that the epithelial cell-ADM-ILC2 connection protected mice from hookworm infections, which damage the lungs and gut.
“ADM is a new target for lung diseases and has been implicated in bacterial pneumonia as well,” says Kronenberg. “But blocking it would have to be done carefully.”
Source: La Jolla Institute for Immunology
Source: Healthcare in Europe