Eczema, hives, quincke edema … Stress reduces the capacity of macrophages, which normally contribute to reducing inflammation, eliminating dead cells from affected areas, which worsens symptoms.
- Psychological stress reduces the capacity of specialized cells, called anti-inflammatory macrophages with programmed death ligand 2 (PD-L2), to eliminate dead cells on the allergy site.
- The accumulation of dead cells, which causes increased eosinophilic infiltration, worsens the allergic response.
- Caspase-1 inhibitors and agents targeting the expression of the CCL24 gene could constitute promising approaches to reduce skin allergies.
“Psychological stress can exacerbate skin allergies, but the underlying mechanisms are misunderstood.” This is why researchers from the universities Juntendo and Okayama (Japan) have decided to carry out a study. As part of their work, Japanese scientists have thus used a model of mouse, IgE-Cai, where the injection of immunoglobulins (IGE) causes persistent inflammation of the ear. The team first identified the neuronal fabric involved in the IgE-Cai through experiences of denervation and destruction of the brain in rodents. The transplantation of immune cells, the sequencing of RNA, flow cytometry were used to detect and characterize immune cells whose operation is altered by stress, then in order to identify the factors contributing to the condition.
Macrophages “forget” how to do their protection work in case of stress
The results, published in the journal Journal of Allergy and Clinical Immunologyhave shown that by disturbing the activity of the β2-Adrenergic (ADRB2) receptor, psychological stress was linked to a decrease in genetic expression in macrophages, immune cells normally helping to reduce inflammation that are responsible for the elimination of dead cells. This process is known as efferocytosis. In addition, the authors found that the accumulation of dead cells in the lesions caused increased infiltration of eosinophiles (a type of white blood cells), which aggravated the allergic response.
Target the expression of the CCL24 gene to reduce skin allergies
Another observation: the accumulation of dead cells on the site of the lesion induces the expression of an eosinophilic recruitment protein, CCL24, which contributes to the aggravation of skin allergies. However, this expression proved to be dependent on the enzymatic activity of caspase-1. Researchers have shown that the administration of an Caspase-1 inhibitor reduced the swelling of the ear caused by the IgE-Cai and reversed eosinophilic infiltration at the lesion. Thus, inhibitors of caspase-1 and agents targeting the expression of the CCL24 gene could constitute promising approaches to reduce skin allergies.
“Stress memory”: “severe stress leaves a persistent imprint on immune cells”
“Our data suggest that the impact of psychological stress on immune cells is durable and can even affect macrophages that are different. This phenomenon, called ‘memory of stress’, implies that severe stress leaves a persistent imprint on Immune cells, influencing their function and contributing to the development of the disease. So does not only shed light on the impact of stress on allergic inflammation, it also lays the basics of an exploration of the way stress exacerbates other diseases involving these macrophages “, has concluded Soichiro Yoshikawawho participated in research.
