The following is a summary of “Transcriptomic profiling of the acute mucosal response to local food injections in adults with eosinophilic esophagitis,” published in the March 2024 issue of Allergy & Immunology by Kleuskens, et al.
Eosinophilic esophagitis (EoE) is characterized by acute mucosal responses triggered by exposure to food allergens, yet the local immune mechanisms underlying these responses are not fully understood. For a study, researchers sought to elucidate the early transcriptomic changes occurring during acute mucosal responses to food allergens in EoE.
Bulk RNA sequencing was conducted on esophageal biopsy specimens from adult EoE patients (n = 5) collected before and 20 minutes after intramucosal injection of various food extracts. Baseline biopsy specimens from control subjects without EoE (n = 5) were also analyzed.
At baseline, EoE patients exhibited increased expression of genes associated with an EoE signature. Following local food injection, 40 genes were identified with potential involvement in the early immune response to food allergens, including CEBPB, IL1B, TNFSF18, PHLDA2, and SLC15A3. These genes were enriched in immune activation processes such as the acute-phase response, cellular responses to external stimuli, and cell population proliferation. TNFSF18, known for its costimulatory effect on T cells, showed the most pronounced dysregulation, with a 12-fold increase compared to baseline and an 18-fold increase compared to negative visual response. Additional experiments suggested that the esophageal epithelium may be a significant source of TNFSF18 in EoE, induced rapidly by costimulation with EoE-relevant cytokines IL-13 and TNF-α.
The study provided unprecedented insight into the transcriptomic changes mediating the acute mucosal immune response to food allergens in EoE. TNFSF18 emerged as a potentially important effector molecule in the response, highlighting its significance in EoE pathogenesis.
Reference: jacionline.org/article/S0091-6749(23)01433-1/fulltext