Amping up allergic responses

According to the Centers for Disease Control and Prevention, over 22 million people in the United States have asthma. Not all patients respond to commonly prescribed medications, including bronchodilators and anti-inflammatory drugs, which suggests that the disease might be driven by distinct mechanisms in different populations of patients. Current research aims to identify common inflammatory mediators, or cytokines, and self-amplifying loops that drive these inflammatory responses. Drugs that target a particular mediator might dampen the allergic response in a broad range of patients and thereby improve the symptoms of asthma.

T cells are a type of immune cell that is produced in response to allergic challenge. T cells of a particular subset, called T helper type-2 (T_H2) cells, are commonly found in the lung following allergic challenge, where they promote both inflammation and hyper-responsiveness of the airways. In a recent study (Immunity 43, 318–330; 2015) Bart N. Lambrecht and colleagues from Ghent University (Belgium) examined how T_H2 cells emerge in the lung following allergic challenge. They sensitized and challenged mice with house dust mites, a common environmental allergen. The frequency of T_H2 cells increased in response to allergen challenge, as did another type of T cell that produces the cytokine interleukin-21 (IL-21).

Using transgenic mice in which cells that produce IL-21 were labeled and tracked with green fluorescent protein, the researchers found that these cells first develop in lymph nodes outside the lung before they are found in the lung. This labeling also confirmed that these cells were the major source of IL-21 within the lung.

Credit: selvanegra/iStock/Thinkstock

These T cells, and the IL-21 that they produce, seem to affect several populations of cells in the lung that have been implicated in asthma. Mice that lack the IL-21 receptor show a lower occurrence of T_H2 cells and eosinophils (another population of cells commonly found in the lungs of asthmatics) following allergic challenge. IL-21 seems to amplify the development and recruitment of these cell types to the lung, and when T cells that produce IL-21 are injected into allergic mice they promote the eosinophil accumulation and airway inflammation. IL-21 itself can also promote expansion of T_H2 cells when injected into mice. Future studies are needed to delineate whether IL-21 acts to sustain the allergic response, and whether it can be targeted in mice with established disease to quell inflammation and reduce hyperresponsiveness in airways.