New drug target for asthma, autoimmune disorders identified

Using a new tool for probing the molecular makeup of cells, researchers have discovered that PD-1 - a marker that already serves as a drug target for some cancers - may also serve as a drug target for asthma and other autoimmune disorders.

The researchers, led by a group from the Wellcome Trust Sanger Institute in the United Kingdom, report their work in the journal Nature.

Immune disorders arise because the immune system either fails - such as by not removing unwanted cells during infection or cancer - or becomes too active.

When it is too active, the immune system attacks healthy cells and tissue, giving rise to autoimmune diseases or allergies such as asthma, where the airways become swollen or inflamed.

In the new study, the researchers examine a recently discovered group of cells in the immune system called innate lymphoid cells (ILC cells). Within this group, there is a subgroup called ILC2 cells that influences immune responses during infections and asthma.

Scientists have observed that levels of ILC2 cells shoot up when triggered by pollen or toxins, causing lung inflammation.

However, as yet, they know little about how ILC2 cells develop from ILC progenitor cells in bone marrow, and whether they sport distinguishing markers once activated.

Mapping development of ILC cells at the molecular level

For the first time, the study team used a new tool called single-cell RNA sequencing to investigate ILC cells.

Fast facts about asthma

  • There is no cure for asthma, but it can be managed with drugs and by avoiding triggers
  • Asthma costs the United States $56 billion per year
  • In 2008 in the U.S., asthma was responsible for 10.5 million missed days of school and 14.2 million missed days of work.

Learn more about asthma

New tools like single-cell RNA sequencing are helping scientists to spot individual differences among genetically similar cells by examining their molecular and protein landscapes as opposed to their genetic blueprints.

Using the new tool, the team probed hundreds of bone marrow cells from mice to study how ILCs develop. They were able to clearly map the different stages of ILC cell progression, starting at the progenitor stage.

They found that the progenitor ILC cells displayed PD-1 protein on their surfaces, and crucially, they found activated ILC2 cells also displayed high levels of PD-1.

The team suggests targeting PD-1 with a simple antibody treatment could be a way to remove these potentially dangerous cells.

PD-1 is already a known target for cancer treatment. In this case, the purpose of the drug is to target the protein on the surface of another group of immune cells called T cells, which normally kill cancer cells.

However, cancer cells have devices that deactivate T cells by attaching specific molecules to their PD-1 surface proteins. Therapies that block PD-1, and thereby deny its use to cancer cells, have already been developed for cancers such as melanoma.

The study team hopes the new discovery about PD-1 in ILC2 cells will improve these existing cancer therapies and also help develop new treatments for asthma and other autoimmune diseases.

"This study helps us understand the biology of the immune system in ways that were impossible previously. If we want to know how to affect the activity of the ILC cells, we need to know how they develop and what switches them on and off.

Not only is this useful for asthma and other inflammatory diseases, it could also help us understand what is happening during PD-1 cancer treatment and could potentially make that cancer therapy more effective."

First author Dr. Yong Yu, Wellcome Trust Sanger Institute

Learn how a PD-1 inhibitor for treating melanoma could change the way lung cancer is treated.

    Single-cell RNA-seq identifies a PD-1hi ILC progenitor and defines its developmental pathway, Yong Yu et al., Nature, doi:10.1038/nature20105, published online 29 September 2016, abstract

    Wellcome Trust Sanger Institute news release, accessed 4 October 2016.

    Additional source: CDC, Asthma's impact on the nation, accessed 4 October 2016.