Asthma is a condition that affects millions worldwide. It has long puzzled researchers and clinicians alike. Despite many advancements in asthma treatment, severe asthma cases continue to pose challenges, particularly in older men. Now, scientists from the University of Southampton and the La Jolla Institute for Immunology (LJI) have made a groundbreaking discovery, shedding light on a unique group of immune cells that may be the culprits behind severe asthma.These immune cells, known as 'cytotoxic CD4+ tissue-resident memory T cells,' appear to congregate in the lungs, particularly in older men who may end up having asthma later in life.For years, the treatment of asthma has primarily focused on general therapies aimed at dampening the immune response. However, this new research reveals that these specialized T cells do not respond to standard treatments. The implications are profound, as identifying these T cells within asthma patients' lungs may indicate a higher risk of hard-to-treat and potentially fatal asthma attacks.The origins of this breakthrough can be traced to the WATCH study. This is an NHS-sponsored study which enrolled numerous patients suffering from asthma. The test group was of varying demographic. This also includes people with differing disease severities.By closely monitoring these patients over an extended period and meticulously analyzing their immune cell populations, researchers have unveiled previously unseen connections between asthma symptoms and immune cell activity.

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Dr. Ramesh Kurukulaaratchy, the director of the WATCH study and an Associate Professor at the University of Southampton, highlights the significance of understanding the role of these T cells. "Once you understand the role of cells like these T cells better, you can start to develop treatments that target those cells," he explained.It is important to note that The T cells in question are classified as "memory" cells due to their ability to react to molecules the body has previously encountered. While memory T cells play a crucial role in safeguarding the body against viruses and bacteria, they pose a significant challenge for asthma patients. These T cells can misinterpret harmless substances, like pollen, and trigger a harmful inflammatory response.One remarkable finding is the high prevalence of these potentially detrimental T cells in men who develop asthma later in life. In an ideal scenario, the lungs should host a diverse array of CD4+ T cell types. However, in this particular group, over 65% of their cells are cytotoxic CD4+ tissue-resident memory T cells.This discovery opens the door to the development of personalized asthma treatments. Through single-cell RNA sequencing, LJI scientists have identified a "biomarker" that can aid in the detection of cytotoxic CD4+ tissue-resident memory T cells in a broader range of patients.Dr. Kurukulaaratchy characterized this as a key breakthrough in asthma research. This is because it moves away from the simplistic categorization of asthma patients into 'T2 high' and 'T2 low' groups. An earlier study by the research team revealed that a vast majority (93%) of the test subjects, who had a severe form of asthma, were categorized into the T2 high categories.Professor Hasan Arshad, an expert in Allergy and Clinical Immunology at the University of Southampton and Director of The David Hide Asthma and Allergy Research Centre, Isle of Wight, underscored the importance of recognizing the diverse subtypes of severe asthma.He emphasized the need to consider severe asthma as encompassing various subtypes, where treatment must be customized according to these categories because a uniform approach is insufficient for all individuals.Moving forward, the researchers aim to leverage sequencing tools and other techniques to uncover additional biomarkers and further refine their understanding of asthma patient subtypes, not only in older men but in other demographic groups. This groundbreaking research offers new hope for tailoring asthma treatment to individual needs, potentially transforming the lives of those affected by this complex condition.

Sources:

Specialized T Cells May Trigger Severe Asthma Attacks in Older MenCytotoxic CD4+ tissue-resident memory T cells are associated with asthma severityAsthma in the elderlyHuman memory T cells: generation, compartmentalization and homeostasis