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Loss of a key immune protein disrupted cell signaling and defense, revealing a novel driver of chronic airway inflammation in NSAID-sensitive disease.  

A study published in June 2025 issue of Journal of Allergy and Clinical Immunology stated that non-steroidal anti-inflammatory drugs (NSAID)-exacerbated respiratory disease (N-ERD) was characterized by chronic asthma, nasal polyposis (NP), and NSAID intolerance, with underlying nasal inflammatory mechanisms remaining insufficiently understood.  

Researchers conducted a retrospective study to examine how apolipoprotein E (ApoE) deficiency in the nasal mucosa influenced macrophage–epithelial cell interaction and inflammatory activation in N-ERD.  

They performed transcriptional and mediator profiling on samples from individuals with N-ERD and used primary human cell cultures to investigate the role of ApoE in both epithelial and myeloid cells. Gene expression and inflammatory mediators were analyzed to understand cellular responses and interactions.  

The results showed that nasal scrapings from individuals with N-ERD had lower APOE expression compared to healthy controls. The APOE levels were inherently low in epithelial cells, while myeloid cells expressed high APOE, which was reduced in monocyte-derived macrophages (MDM) from N-ERD cases. Knockdown (kd) of APOE using siRNA in these macrophages led to increased expression of CXCL7. Additionally, oxidized arachidonyl-phosphatidylethanolamine levels were elevated in APOE-deficient macrophages, and ApoE was found to protect against ferroptotic cell death.  

Investigators concluded that myeloid ApoE played a regulatory role in macrophage–epithelial cell interaction and ferroptosis, and its deficiency contributed to sustained type 2 inflammation in N-ERD. 

Source: jacionline.org/article/S0091-6749(25)00652-9/fulltext