A pioneering study from Juntendo University and Okayama University explains how stress impairs immune cell function, worsening skin allergies by preventing the clearance of dead cells. This groundbreaking research has significant implications for treating stress-related inflammatory diseases.
Psychological stress is widely known to exacerbate skin allergies, but the complex molecular mechanisms underlying this phenomenon have been elusive — until now. Researchers from Japan have made a significant discovery, shedding light on how stress interferes with immune responses, leading to deteriorating allergic symptoms.
The study, published in The Journal of Allergy and Clinical Immunology, was conducted by researchers from the Juntendo University Graduate School of Medicine and the Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences.
Their work focuses on IgE-mediated cutaneous allergic inflammation (IgE-CAI), a model characterized by swelling and immune cell infiltration at allergy sites. The team discovered that stress reduces the ability of specialized anti-inflammatory cells, known as PD-L2-positive macrophages, to clear dead cells from the site of inflammation.
“This study is the first in the world to demonstrate that stress, through the sympathetic nervous system, disrupts macrophage function, which normally helps suppress allergic reactions, thereby intensifying allergic responses,” co-lead author Soichiro Yoshikawa, an associate professor at the Juntendo University Graduate School of Medicine, said in a news release.
Using a mouse model of IgE-CAI, the researchers noted that psychological stress linked to decreased gene expression in macrophages responsible for dead cell clearance, a process called efferocytosis. This led to dead cell accumulation, triggering increased infiltration of eosinophils, immune cells responsible for allergic inflammation.
Further analysis revealed that stress impacts the activity of the β2-adrenergic receptor (Adrb2) in macrophages, impairing their function. As a result, macrophages exposed to stress exhibited reduced efferocytosis, worsening skin allergy symptoms.
“Our findings suggest that the impact of psychological stress on immune cells is long-lasting and can even affect macrophages that differentiate later. This phenomenon, referred to as ‘stress memory,’ implies that severe stress leaves a lingering imprint on immune cells, influencing their function and contributing to disease development,” added Yoshikawa.
Moreover, the study identified that dead cell accumulation stimulates CCL24 protein expression, attracting eosinophils to the inflammation site, thereby worsening allergic responses. However, blocking caspase-1 enzyme activity reduced this effect, opening potential avenues for therapeutic interventions.
“Anti-inflammatory macrophages play crucial roles in various diseases, including cancer, autoimmune disorders and wound healing. This study not only sheds light on the impact of stress on allergic inflammation but also lays the groundwork for exploring how stress exacerbates other diseases involving these macrophages,” Yoshikawa added.
Understanding stress-induced immune cell dysfunction offers promising prospects for novel treatments targeting stress-related inflammatory diseases. Providing insights into stress memory and its lasting effects on the immune system could pave the way for groundbreaking therapeutic strategies.