In a study*, the researchers suppressed the production of these cells while the irritated skin was exposed to an allergen. Consequently, the resulting inflammatory reaction did not lead to hypersensitivity in the animals’ lungs toward the same allergen. Their subsequent review article** discusses the broader implications of these findings for asthma prevention.
Eczema, also known as atopic dermatitis, is one of the most common skin diseases. It usually begins during infancy or early childhood. The cause is not yet fully understood. However, allergens from animal hair, house dust or pollen can trigger flare-ups of the condition. “Atopic eczema disrupts the skin barrier, enabling substances from the environment to enter the body more easily,” explains Prof. Dr. David Vöhringer, Director of the Department of Infection Biology at Universitätsklinikum Erlangen.
As children grow up, they often additionally develop allergic asthma or food allergies. All these conditions are known as “atopic” diseases that are characterized by hypersensitivity of the skin or mucous membranes. “In medicine, the development of these diseases is often referred to as an atopic march,” says Dr. Daniel Radtke, head of the study and co-author of both publications with his team member Dr. E Da Choi, and Prof. Vöhringer. “What causes allergic sensitization to spread to other organs is not yet fully understood.”
The research group recently showed, however, that certain immune cells, the basophils, play an important role in the atopic march . They are produced by stem cells in the bone marrow and normally circulate in the blood. When the skin is irritated by a foreign substance, the basophils cross the blood vessel wall and migrate to the affected tissue. There they release signaling molecules that activate other immune cells. The result is an inflammatory response .
“We applied an allergen to the skin of mice with atopic dermatitis symptoms and simultaneously suppressed the formation of basophils for a short period,” explains Dr. Radtke. When the animals later inhaled the allergen, the lungs showed only a weak inflammatory response. In a control group in which the team had not suppressed basophil production, the response was markedly stronger – similar to a severe asthma attack.
“This shows that basophils in the skin cause the lung to become hypersensitive to the allergen as well,” says Dr. Radtke. “We do not yet know how this happens.” A signaling molecule called interleukin‑4 may play an important role. It is released in large amounts by basophils when they are activated by an allergen, and it amplifies the immune response. Components of this strong immune response can reach the airways via the bloodstream and put the local immune system or the cells lining the bronchi on heightened alert.
In their newly published review article, the researchers point out that their findings could also lead to new preventive strategies against asthma. “It is very important to treat allergic skin reactions quickly and effectively in early childhood,” emphasizes Prof. Vöhringer. “This is because prolonged or very strong activation of basophils could significantly increase the risk of asthma.” It may also be possible to specifically block the “remote effect” of this activation. To do this, it is important to determine the molecular pathways through which the cells communicate with the lung.
Drugs are currently being developed and tested that reduce interleukin‑4 production by basophils. The primary goal is to use these agents to relieve the skin condition and its extremely unpleasant itching. “Perhaps it may also be possible to reduce the risk of patients developing asthma later in life with these agents,” hopes Prof. Vöhringer. “Whether that is the case remains to be seen.”
Frontiers in Immunology