Recent research has unveiled the molecular mechanisms by which psychological stress exacerbates skin allergies. Using a mouse model of IgE-mediated allergic inflammation, scientists demonstrated that stress disrupts immune functions, worsening allergic symptoms by interfering with the body's inflammatory responses.
The study, led by Professor Soichiro Yoshikawa and colleagues from Juntendo University and Okayama University, was published in The Journal of Allergy and Clinical Immunology. It found that stress reduces the ability of macrophages—immune cells that help clear dead cells—from effectively managing allergic inflammation, leading to increased symptoms.
In the experiment, researchers injected IgE into mice, inducing persistent ear inflammation. They identified nerve tissue involved in this response and assessed immune cells and contributing factors. The findings revealed that stress correlates with decreased gene expression in macrophages responsible for phagocytosing dead cells, a process known as efferocytosis.
Moreover, the accumulation of dead cells at the site of inflammation resulted in heightened eosinophil infiltration, further aggravating allergic reactions. Macrophages expressing PD-L2 play a critical role in maintaining anti-inflammatory functions through the clearance of dead cells. However, stress was shown to impair their function by disrupting β2-adrenergic receptor (Adrb2) activity.
The research highlights that the impact of psychological stress on immune cells can be long-lasting, potentially affecting macrophages that differentiate later. This phenomenon, termed “stress memory,” suggests that intense stress leaves a lasting imprint on immune cells, influencing their function and contributing to disease development.
Additionally, the study found that dead cell accumulation at the inflammation site induced the expression of the eosinophil-attracting protein CCL24, worsening skin allergies. This expression was dependent on caspase-1 enzyme activity. The introduction of a caspase-1 inhibitor reduced ear swelling caused by IgE and reversed eosinophil infiltration at the site.
These results indicate that caspase-1 inhibitors and agents targeting CCL24 gene expression may offer promising strategies for alleviating skin allergies. Yoshikawa emphasized the significance of anti-inflammatory macrophages in various diseases, including cancer and autoimmune disorders, suggesting that the study not only illuminates the effects of stress on allergic inflammation but also lays the groundwork for exploring how stress exacerbates other diseases linked to these immune cells.
While complete stress avoidance is ideal for preventing immune cell dysfunction, understanding the molecular mechanisms behind stress memory may lead to therapeutic strategies that mitigate or reverse these effects, potentially resulting in new treatment methods for stress-related diseases with broad implications in clinical research.