Researchers from the University of Leicester and University Hospitals of Leicester NHS Trust, working with the National Institute of Allergy and Infectious Diseases (NIAID) and Genentech, have discovered new insights into how asthma may be caused, by identifying three distinct groups of asthma patients characterised by the activity of different genes in an individual's airways.
Asthma affects about five million people in the UK. Not all patients respond the same way to current treatments, suggesting that asthma is more than a single disease. Drugs that target specific molecules in the lungs suggest that the typical symptoms of asthma can be caused by different processes.
In the study, titled 'Th2 and Th17 inflammatory pathways are reciprocally regulated in asthma' which is published in the journal Science Translational Medicine, University of Leicester researchers led by Professor Peter Bradding from the Department of Infection, Immunity and Inflammation, in collaboration with Genentech, looked prospectively at lung samples from 51 asthma patients who had a range of disease severity and identified three different clusters in the airways called Th2-high, Th17-high, and Th2/17-low.
Patients exhibited either high Th2 or high Th17 activity, or low activity of both pathways. Interestingly, no patients had simultaneously high Th2 and Th17 activity, indicating that these pathways are somehow mutually exclusive.
The research team at NIAID in the USA found in a mouse model of asthma that when Th2-activity was inhibited this promoted Th17 activity. When Th2 and Th17 were simultaneously blocked in the mouse model of asthma, the researchers observed greater benefit than blocking one pathway alone, suggesting that new therapies targeting both pathways may demonstrate better efficacy than targeting either pathway alone.
Professor Peter Bradding from the University of Leicester's Department of Infection, Immunity and Inflammation said: "This research gives new insight into the molecular mechanisms that drive asthma. Because new treatments that block Th2 pathways may promote Th17 pathways, it may be more effective to block both at the same time, rather than either alone. This can be tested in future research trials in patients."
Overall, gaining a better understanding of how these immune pathways cross-regulate in people will advance therapeutic research for asthma and other inflammatory diseases.
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The research in Leicester was funded by Asthma UK, the National Institute for Health Research (NIHR), and Genentech, Inc. and was supported by the NIHR Leicester Respiratory Biomedical Research Unit.
Notes to Editors:
To arrange interviews with Professor Peter Bradding please contact Jeanette Garnett on jeanette.garnett@uhl-tr.nhs.uk or call 0116 258 3998
The National Institute for Health Research (NIHR) is funded by the Department of Health to improve the health and wealth of the nation through research. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the Government's strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world. For further information, visit the NIHR website.
Journal
Science Translational Medicine