New insights into rare immune cell populations reveal sex differences and treatment effects in severe asthma

Researchers Dr Kyle Mincham and Professor Robert Snelgrove at Imperial’s National Heart and Lung Institute have uncovered important differences in how a group of immune cells, called innate lymphoid cells (ILCs), behave in people with severe asthma.

ILCs, which can be broadly classified into 3 types, help maintain tissue health but can contribute to disease when they become unbalanced. Using advanced high-parameter flow cytometry, the team studied ILCs in blood and airway samples from healthy individuals and asthma patients, including those receiving targeted therapies.

Published in Science Translational Medicine, the study revealed that ILCs are highly heterogeneous and plastic, changing their characteristics depending on tissue location, sex, and disease state. Notably, females with severe asthma had higher levels of certain ILC types compared with males, potentially attributable to suppressive effects of testosterone on ILC progenitors. In the airways, all ILC types were increased in asthma patients, with elevated levels of group 2 ILCs (ILC2) associated with poorer lung function.

The research also provides insight into how targeted asthma treatments work. Therapies aimed at IL-5 and its receptor were found to reduce inflammatory ILC2 subsets without altering the overall number of ILCs, suggesting a mechanism for their effectiveness in controlling severe asthma.

Dr Kyle Mincham, Imperial College Research Fellow, said, “These findings provide novel, in-depth insight into a rare but important population of immune cells, highlighting how sex and tissue microenvironment shape their functionality in severe asthma.  These studies support the premise that perturbations in the ILC landscape contribute to pathogenesis of severe asthma, and that comprehensive profiling of ILCs could support new personalised treatment strategies. These studies also improve understanding of how IL-5-targeting therapies work and may inform future approaches for better disease control.”