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La Jolla, CA – Scientists at the La Jolla Institute for Immunology (LJI) have made a significant stride in asthma treatment, developing therapeutic “cocktails” that promise long-lasting relief for those suffering from treatment-resistant asthma and other inflammatory immune system diseases.
Published in the Journal of Allergy and Clinical Immunology, the study details the creation of two therapeutic combinations designed to prevent immune cells from overreacting to allergens. These cocktails target key molecules—ICOSL, OX40L, and CD30L—that enable tissue-resident memory T cells to remain active and persist in high numbers within tissues. By inhibiting these molecules, the T cells are prevented from triggering asthma attacks and do not persist to cause future exacerbations.
“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.
The researchers demonstrated that either a combination of ICOSL and OX40L inhibitors or ICOSL and CD30L inhibitors effectively treated a mouse model of severe allergic asthma. This offers the potential for doctors to tailor treatment to individual patients with different forms of allergic asthma.
“This study gives us insight into what could be two terrific options for helping asthma patients, but also might be applicable to other inflammatory diseases as well as autoimmune diseases,” added Dr. Michael Croft, senior author of the study.
The research builds on a previous study that showed blocking OX40L and CD30L could reduce asthma attacks in mice. The new study identified ICOSL as another crucial molecule involved in the persistence of tissue-resident memory T cells, which play a significant role in long-lasting, exaggerated allergic responses.
The team found that blocking ICOSL alongside either OX40L or CD30L significantly reduced the number of these memory T cells in the lungs, leading to weeks of protection against asthma exacerbations in mice.
The researchers are now focusing on further reducing the remaining memory T cells and advancing these therapeutic cocktails to clinical trials. They also believe these findings could have implications for treating other autoimmune diseases, such as multiple sclerosis, atopic dermatitis, and inflammatory bowel disease.
“The combination therapies that we have discovered might then pave the way for durable as well as effective treatments for multiple immune system diseases,” said Croft.
This research was funded by the Tullie and Rickey Families SPARK Awards for Innovations in Immunology program.
Reference: “ICOSL, OX40L, and CD30L Control Persistence of Asthmatic CD4 Trm cells” by Gurupreet S. Sethi, Ashmitaa Logandha Ramamoorthy Premlal, Ashu Chawla and Michael Croft, 6 February 2025, Journal of Allergy and Clinical Immunology. DOI: 10.1016/j.jaci.2024.12.1097
Disclaimer: This article is based on research findings in a mouse model and is intended for informational purposes only. The therapies described are still in the pre-clinical stage and have not been approved for use in humans. Further research and clinical trials are necessary to determine their safety and efficacy in human patients. This information should not be used as a substitute for professional medical advice. Always consult with a qualified healthcare provider for any health concerns or before making any decisions related to your health or treatment.
