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Asthma attacks in older men could be triggered by immune cells


Southampton researchers are part of an international team that has identified an immune cell responsible for some hard-to-treat asthma cases.


The researchers uncovered a group of immune cells that may drive severe asthma. These cells gather in the lungs, and appear to cause the most harm in men who develop asthma in later life.


Dr Ramesh Kurukulaaratchy and Professor Hasan Arshad at the NIHR Southampton Biomedical Research Centre were involved in the study. It was led by researchers at The La Jolla Institute for Immunology (LJI) in California.


Hundreds of volunteers


They identified the immune cells thanks to volunteers enrolled in the NHS clinic-based WATCH study. They are called cytotoxic CD4+ tissue-resident memory T cells.


The WATCH study is led by Dr Ramesh Kurukulaaratchy, Associate Professor at the University of Southampton. It follows hundreds of asthma patients of different ages, sexes and disease severities over many years.


Researchers are using the study to make new connections between asthma symptoms and immune cell activity. It is supported by the NIHR Southampton Biomedical Research Centre and NIHR Southampton Clinical Research Facility.


"Once you understand the role of cells like these T cells better, you can start to develop treatments that target those cells," says Dr Kurukulaaratchy.


The researchers now hope to learn more about these cells and their role in asthma, to develop personalised therapies for patients.


Unresponsive to treatment


The new research is published in the journal Med. It suggests patients with these cells in their lungs may be more likely to have hard-to-treat, and potentially fatal, asthma attacks.


Doctors usually give asthma patients a general therapy to dampen their immune response. But these cells don't respond to this treatment.


Prof Pandurangan Vijayanand and Prof Gregory Seumois at LJI co-led the study.

"If you are male and you develop asthma after age 40, there's a high chance this T cell population is in your lungs," says Prof Seumois.


How harmful T cells drive asthma


The T cells are called 'memory' cells because they react to molecules that the body has previously fought off. They help protect the body from viruses and bacteria.


But this 'memory' is a big problem for asthma patients. Their misguided T cells trigger a dangerous inflammatory response to harmless molecules like pollen.


Men who developed asthma later in life had an overwhelming number of these potentially harmful T cells. In this group, more than 65 percent of their CD4+ T cells were this type.


Personalised asthma treatments


The researchers used single-cell RNA sequencing to identify the cytotoxic CD4+ tissue-resident memory T cells. This method could help detect these cells in more patients going forward.


This represents a 'paradigm shift' in asthma research, says Dr Kurukulaaratchy. Before now, scientists and clinicians separated asthma patients into just two groups: ‘T2 high’ and T2 low’.


In a study published earlier this year, the team showed the importance of identifying more asthma patient subgroups. They found 93 percent of WATCH participants with severe asthma were in the T2 high category.


Professor Hasan Arshad is Chair in Allergy and Clinical Immunology at the University of Southampton, and Director of The David Hide Asthma and Allergy Research Centre, Isle of Wight.


He says: “We have to think of severe asthma as having different subtypes. The treatment has to be tailored according to these subtypes, because one size does not fit all."


The researchers now want to use sequencing tools and other techniques to discover more asthma patient subtypes.

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