25 Jun DUKE-NUS Scientists Discover Novel Mechanism Allergens Use to Release Histamine from Mast Cells
MedicalResearch.com Interview with:
Prof. Abraham
Professor Soman Abraham PhD
Grace Kerby Distinguished Professor of Pathology
Duke University.
Dr. Abraham led the research when working in the Emerging Infectious Diseases Research Programme
at Duke-NUS Medical School in Singapore
MedicalResearch.com: What is the background for this study?
Response: The degranulation of mast cells (MCs) is a process that leads to allergic symptoms, ranging from itching, redness, and swelling of the tissue to severe and potentially life-threatening anaphylaxis involving multiple organ systems. According to the World Health Organization (WHO), more than 10 per cent of the global population suffers from food allergies. As allergy rates continue to rise, so does the incidence of food-triggered anaphylaxis and asthma worldwide. In view of the fact that allergic diseases are difficult to prevent or treat, we sought to understand the underlying basis for anaphylactic reactions.
MedicalResearch.com: What are the main findings?
Response: The team led by Professor Soman Abraham at Duke-NUS has discovered a novel mechanism of anaphylactic MC degranulation triggered by allergens. This mechanism involves two members of an intracellular multiprotein complex called the inflammasome—NLRP3 and ASC—which aggregate on intracellular MC granules, forming a unique protein complex termed the ‘granulosome’. Following activation of MCs by allergens, the granulosomes moves to the MC cell surface resulting in extracellular release of MC granules. Previously, these inflammasome proteins were only known to spontaneously assemble within immune cells to secrete soluble chemicals that alert other parts of the immune system upon detecting an infection. This new discovery reveals a new function for inflammasome proteins in MCs during allergic anaphylaxis.
MedicalResearch.com: Are there any medications that block inflammasome production or activation?
Response: Having demonstrated the role of NLRP3 and ASC in trafficking mast cells granules to the cell surface, the team then investigated known inflammasome inhibitors to determine their efficacy in preventing this event. The authors revealed that using an inflammasome-blocking drug similar to those undergoing clinical trials for chronic inflammatory diseases, called CY-09, effectively impedes IgE–Ag-induced MC degranulation. By employing interaction domain mapping, they demonstrated that CY-09, which binds to NLRP3, inhibits its binding to the main MC granule membrane component, CD63. Furthermore, in their preclinical model, they effectively prevented anaphylactic shock with this drug. This breakthrough holds tremendous translational potential and represents a paradigm shift, not only for further research but also in enhancing the quality of life for those at risk of severe allergic reactions.
MedicalResearch.com: What should readers take away from your report?
Response: The critical takeaway is that inflammasome components NLRP3 and ASC have a hitherto underappreciated role in the degranulation process of mast cells and that targeting these components might offer a therapeutic route for preventing severe inflammatory responses such as anaphylaxis.
MedicalResearch.com: What recommendations do you have for future research as a results of this study?
Response: Future research should explore the dosage and frequency of use of this NLRP-3 inhibitor to achieve the best protective effects against anaphylactic shock in humans.
MedicalResearch.com: Is there anything else you would like to add? Any disclosures?
Response: For detailed disclosures, acknowledgments, and funding sources, readers should refer to the full publication. For further details and specific data points, readers should refer to the published article: “Anaphylactic degranulation by mast cells requires the mobilization of inflammasome components” in Nature Immunology, Volume 25, April 2024, pages 693-702. Mencarelli, A., Bist, P., Choi, H.W. et al. DOI: 10.1038/s41590-024-01788-y.
Citation: Mencarelli, A., Bist, P., Choi, H.W. et al. Anaphylactic degranulation by mast cells requires the mobilization of inflammasome components. Nat Immunol 25, 693–702 (2024). DOI: 10.1038/s41590-024-01788-yThe information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition.
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Last Updated on June 25, 2024 by Marie Benz MD FAAD