Thursday 28 September 2023

Blocking immune system 'messenger' may treat severe asthma

 Asthma is more dangerous than many people realize. An estimated 10 Americans die every day from asthma, and the disease leads to around 439,000 hospitalizations and 1.3 million emergency room trips each year.

"Asthma is one of the most important allergic diseases to study," says Professor Toshiaki Kawakami, M.D., Ph.D., a member of the Center for Autoimmunity and Inflammation at La Jolla Institute for Immunology (LJI).

In a new study, Kawakami and his colleagues at LJI investigated the molecular drivers of severe asthma and rhinovirus-induced asthma exacerbation (a type of asthma that can accompany a common cold). Their findings, published recently in The Journal of Allergy and Clinical Immunology, suggest people with both types of asthma may benefit from therapies that block interactions between a molecule called histamine-releasing factor (HRF) and antibodies called immunoglobulin E (IgE).

As Kawakami explains, many people with severe asthma aren't responsive to current asthma therapies. He hopes two potential drug strategies from his laboratory might inhibit HRF and IgE interactions and deliver relief for these patients. "We hope this approach can be a means of treating severe asthma and asthma exacerbation," he says.

The problem with histamine-releasing factor

Immune cells work as a team, and they secrete molecules to "talk" to each other. One of these molecular messengers is HRF, which is made by many types of cells, including lung epithelial cells and immune cells called macrophages. When a person encounters an allergen, these cells start churning out more HRF. The HRF then courses through the body and looks for special antibodies to bind to. HRF has several different kinds of antibody partners, however, and each interaction sends a different message to the surrounding immune cells.

Kawakami and his colleagues are working to understand how these HRF and antibody interactions drive dangerous allergic reactions. Over the last decade, the researchers have shown that HRF interactions with the IgE antibody drive harmful inflammation in mouse models of asthma.

 sources: sciecnce daily

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