A research group led by Yuri Tachibana (Ph.D. candidate at the time of research) at the University of Tokyo Graduate School discovered that the concentration of a lipid called 12-HETE increased significantly in the nasal cavities of mice with symptoms of allergic rhinitis.Suppression of the production of this substance alleviated allergic symptoms.
Allergic rhinitis such as hay fever has immediate symptoms, such as sneezing and runny nose, that appear immediately after antigen stimulation, and delayed symptoms, such as nasal congestion, that appear several hours later.Drugs are less effective against late-onset symptoms, causing sleep disturbances and reduced work efficiency, which greatly reduces the patient's quality of life (QOL). have been sought after.
Therefore, the research group administered ovalbumin (allergen) to mice to create model mice exhibiting symptoms of allergic rhinitis.When nasal secretions from these mice were collected and analyzed, a marked increase in the concentration of a lipid called 12-HETE (an unsaturated fatty acid) was confirmed.
Since 12-HETE synthase ALOX12 was expressed in eosinophils infiltrating the nasal mucosa, mice were given an ALOX12 inhibitor.As a result, symptoms of rhinitis including infiltration of inflammatory cells improved.Subsequent administration of 12-HETE to these mice recurred rhinitis symptoms.As a mechanism for this, we found that 12-HETE strongly promotes the differentiation and infiltration of T cells that exacerbate allergic symptoms.
These results suggest that eosinophils infiltrating the nasal mucosa produce 12-HETE when allergic rhinitis develops, which promotes differentiation of T cells and exacerbates rhinitis symptoms. A study using a mouse model revealed that delayed-onset symptoms were suppressed and allergic symptoms were alleviated. Suppression of 12-HETE production could be a breakthrough therapy.
Paper information:[Allergy] 12-HETE promotes late-phase responses in a murine model of allergic rhinitis
