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February 2025 – La Jolla, CA – Scientists at La Jolla Institute for Immunology (LJI) are making strides in the development of a novel therapeutic approach that could provide long-lasting relief for individuals suffering from treatment-resistant asthma. According to a recent study published in the Journal of Allergy and Clinical Immunology, this breakthrough could also have broader applications in managing immune inflammation associated with other diseases.
A Game-Changer in Asthma Treatment
Researchers at LJI have engineered two therapeutic “cocktails” designed to prevent immune cells from overreacting to allergens. These cocktails work by inhibiting specific molecules—ICOSL, OX40L, and CD30L—which play a crucial role in maintaining high numbers of tissue-resident memory T cells in lung tissues. By blocking these molecules, the therapy effectively prevents asthma attacks and reduces the persistence of inflammatory responses.
The study demonstrated that either of the two therapeutic combinations—ICOSL and OX40L inhibitors or ICOSL and CD30L inhibitors—were effective in reducing severe allergic asthma symptoms in a mouse model. This development offers potential flexibility for tailoring treatments to different asthma subtypes.
“If we can target these molecules in human patients, they might be able to develop long-lasting tolerance to allergens,” said Dr. Gurupreet Sethi, the study’s first author and an instructor at LJI.
Beyond Asthma: A New Avenue for Inflammatory Disease Treatment
Senior study author Dr. Michael Croft, a professor at LJI’s Center for Autoimmunity and Inflammation, highlighted the broader implications of the research. “This study not only provides insight into potential new asthma treatments but may also be applicable to other inflammatory and autoimmune diseases.”
Previous research from the Croft Lab in 2020 identified OX40L and CD30L as key contributors to asthma attacks. However, this new study builds upon those findings by incorporating ICOSL, which appears to play an additional role in the regulation of lung inflammation.
By analyzing single-cell sequencing data, researchers discovered that memory T cells in asthmatic lungs exhibit significant variability. Some of these cells, known as tissue-resident memory T cells, contribute disproportionately to inflammation. The latest findings suggest that blocking ICOSL alongside OX40L or CD30L leads to a greater reduction in these harmful immune cells—cutting their presence in lung tissues by up to 80%.
A Path to Lasting Relief
Following treatment with the therapeutic cocktails, mice remained protected against asthma exacerbations for weeks, even after repeated exposure to allergens. The research suggests that this therapy could erase the immune system’s memory of asthma triggers, potentially providing long-term benefits for asthma patients.
Dr. Sethi emphasized the importance of refining this approach further. “Reducing the remaining 20% of allergic tissue-resident memory T cells is the next step in our research. We are also looking to advance these therapies into clinical studies.”
Beyond asthma, the study’s findings could have significant implications for other inflammatory diseases. Similar memory T cells accumulate in patients with conditions such as multiple sclerosis, atopic dermatitis, and inflammatory bowel disease. By limiting the number of these immune cells, researchers believe they may be able to prevent disease flare-ups and provide more effective treatments for a variety of conditions.
“This combination therapy could pave the way for durable and effective treatments for multiple immune system diseases,” Dr. Croft concluded.
Looking Ahead
The researchers plan to further investigate these therapeutic combinations in human clinical trials. If successful, these therapies could revolutionize treatment options for millions of people suffering from chronic inflammatory diseases.
Disclaimer:
This article is based on scientific research and is for informational purposes only. The therapies discussed are still in experimental stages and are not yet approved for clinical use. Individuals should consult healthcare professionals for medical advice and treatment options.
